Ribavirin Aerosol Research Articles

Clinico-Virological Outcomes and Mutational Profile of SARS-CoV-2 in Adults Treated with Ribavirin Aerosol for COVID-19 Pneumonia.

The emergence of new SARS-CoV-2 variants can affect vaccine efficacy, laboratory diagnosis and the therapies already available, triggering interest in the search for antiviral agents for SARS-CoV-2 infections. Ribavirin (RBV) is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including SARS-CoV-2. This retrospective study evaluated the dynamics and viral clearance of SARS-CoV-2 in hospitalised adult participants (PTs) with COVID-19 pneumonia who received an RBV aerosol within a compassionate use study. The impact of RBV on the clinical outcome and the mutational profile of SARS-CoV-2 was also assessed. The median RNA values measured in nine PTs included in this study decreased from baseline to discharge (at BL, threshold cycle (Ct) = 22.4, IQR 19.84-5.07; at discharge, Ct = 27.92, IQR 26.43-36.11), with a significant decline in the Ct value evaluated by Friedman rank ANOVA analysis, p = 0.032. Seven out of nine PTs experienced a clinical improvement, while two PTs deceased during hospitalisation. In PTs with a favourable outcome, the virus clearance rate at discharge was 28.6%. The cumulative clearance rate was 71.4% within 14 days from discharge. A mutational pattern after RBV was detected in three out of five PTs in whom whole-genome sequencing was available. Our findings suggest that RBV limits SARS-CoV-2 replication, possibly resulting in a favourable clinical outcome. Ribavirin may also contribute to the mutational spectrum of SARS-CoV-2.

Clinical comprehensive evaluation of Houyanqing Oral Liquid in treatment of acute pharyngitis

This study systematically combed the existing evidence of Houyanqing Oral Liquid in the treatment of acute pharyngitis from the "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM) and carried out qualitative and quantitative analysis of the data from each dimension. The multi-criteria decision analysis(MCDA) model and CSC v2.0 were used to evaluate the clinical value of this drug, so as to provide evidence for the selection of essential drugs in the department of otolaryngology and for medical and health decision-making. The dimensions are graded A, B, C, or D. The adverse reactions of Houyanqing Oral Liquid in the treatment of acute pharyngitis were mainly manifested as abdominal pain, diarrhea, rash, etc., which were relieved after drug withdrawal. In terms of safety, it was considered that Houyanqing Oral Liquid had controllable risk and high safety, which was rated as grade B. Compared with ribavirin aerosol alone, Houyanqing Oral Liquid combined with ribavirin aerosol can significantly improve the total response rate, shorten the time to abatement of fever and di-sappearance of throat pain and mucosal congestion, and alleviate mucosal congestion and cough with sputum. With medium-quality evidence, the effectiveness was rated as grade B. Compared with ribavirin aerosol alone, Houyanqing Oral Liquid combined with ribavirin aerosol had cost-effectiveness advantages in the treatment of acute pharyngitis, and its economy was rated as grade C with the evidence of general quality. For acute pharyngitis, Houyanqing Oral Liquid can shorten the disease course and obviously relieve sore throat. Moreover, it can be used for the treatment of radioactive pharyngitis and oral ulcer, and thus its innovation was rated as grade B. With convenient and simple administration and standard and complete drug information, the suitability of this drug was rated as grade B. Houyanqing Oral Liquid is derived from the folk prescription in Hunan province and has been subjected to real-world studies, and thus the TCM characteristics was rated as grade B. According to the ratings of all the dimensions, the comprehensive value of Houyanqing Oral Liquid in the clinical treatment of acute pharyngitis was determined as grade B, with sufficient evidence and clear results. It is suggested that the results should be conditionally converted into relevant policy of clinical basic drug management according to procedures.

Design, synthesis, and anti-respiratory syncytial virus potential of novel 3-(1,2,3-triazol-1-yl)furoxazine-fused benzimidazole derivatives

Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in infants, children, and older persons. Currently, the only approved anti-viral chemotherapeutic drug for RSV treatment is ribavirin aerosol; however, its significant toxicity has led to restricted clinical use. In a previous study, we developed various benzimidazole derivatives against RSV. In this study, we synthesised 3-azide substituted furoxazine-fused benzimidazole derivatives by sulfonylation and azide substitution of the 3-hydroxyl group of the furoxazine-fused benzimidazole derivatives. Subsequently, a series of 3-(1,2,3-triazol-1-yl)-substituted furoxazine-fused benzimidazole derivatives were synthesised using the classical click reaction. Biological evaluations of the target compounds indicated that compound 4a-2 had higher activity against RSV (EC50 = 12.17 μM) and lower cytotoxicity (CC50 = 390.64 μM). Compound 4a-2 exerted anti-viral effects against the RSV Long strain by inhibiting apoptosis and the elevation of reactive oxygen species (ROS) and inflammatory factors caused by viral infection in vitro. Additionally, the clinical symptoms of the virus-infected mice were markedly relieved, and the viral load in the lung tissues was dramatically decreased. The biosafety profile of compound 4a-2 was also favourable, showing no detectable adverse effects on any of the major organs in vivo. These findings underscore the potential of compound 4a-2 as a valuable therapeutic option for combating RSV infections while also laying the foundation for further research and development in the field.

A randomized, placebo-controlled study to evaluate safety and pharmacokinetics of inhaled ribavirin.

Ribavirin is an inosine monophosphate dehydrogenase inhibitor. Studies suggest ribavirin aerosol could be a safe and efficacious treatment option in the fight against coronaviruses. However, current treatment is long (12–18 h per day, 3–7 days), limiting clinical utility. A reduction in treatment time would reduce treatment burden. We aimed to evaluate safety and pharmacokinetics (PK) of four, single‐dose regimens of ribavirin aerosol in healthy volunteers. Thirty‐two subjects were randomized, to four cohorts of aerosolized ribavirin (active) or placebo. Cohort 1 received 50 mg/ml ribavirin/placebo (10 ml total volume); cohort 2, 50 mg/ml ribavirin/placebo (20 ml total volume); cohort 3, 100 mg/ml ribavirin/placebo (10 ml total volume); and cohort 4, 100 mg/ml ribavirin/placebo (20 ml total volume). Intense safety monitoring and PK sampling took place on days 1, 2, 3, and 40. Subjects were (mean ± SD, active vs. placebo) aged 57 ± 4.5 vs. 60 ± 2.5 years; 83% vs. 88% were female; and 75% vs. 50% were Caucasian. Some 12.5% (3/24) and 25% (2/8) experienced at least one treatment‐emergent adverse event (TEAE) (two moderate; five mild) in the active and placebo groups, respectively. No clinically significant safety concerns were reported. Mean maximum observed concentration (C max) and area under the curve (AUC) values were higher in cohort 4, whereas cohorts 2 and 3 showed similar PK values. Ribavirin absorption reached C max within 2 h across cohorts. Four single‐dose regimens of ribavirin aerosol demonstrated systemic exposure with minimal systemic effects. Results support continued clinical development of ribavirin aerosol as a treatment option in patients with coronaviruses.

Ribavirin Aerosol in the Treatment of SARS-CoV-2: A Case Series.

Ribavirin is an inosine monophosphate dehydrogenase inhibitor with demonstrated activity against coronaviruses, including SARS-CoV-2. Five hospitalized patients with COVID-19 (confirmed by positive tests for SARS-CoV-2) received treatment with ribavirin for inhalation solution (ribavirin aerosol) as part of a compassionate use program. Patients included four men and one woman, with an age range of 29–72 years. Patients were managed according to international and Italian treatment guidelines for COVID-19. In addition, therapy with ribavirin aerosol 100 mg/mL was administered for 30 min twice daily for 6 days (i.e., 12 doses) in all patients. In order to address concerns about a possible increase in viral dispersal with the use of a nebulizer, healthcare providers remained outside the patient room during ribavirin aerosol administration. Pretreatment chest computed tomography (CT) scans showed pseudonodular areas of parenchymal thickening in the upper right lobe with associated ground glass opacities, multiple areas of parenchymal consolidation in both lower lobes with associated ground glass opacities, bilateral parenchymal thickening and multiple associated ground glass areas, or focal ground glass areas in the upper lobes bilaterally, which were almost completely resolved (three patients) or moderately cleared (one patient) on imaging at the end of ribavirin treatment. For a fifth patient, CT scans showed a stable pulmonary picture at the end of ribavirin treatment. No adverse reactions to ribavirin treatment were observed in any of the five patients. All patients recovered fully, and nasopharyngeal swabs obtained after hospital discharge tested negative for SARS-CoV-2. Ribavirin aerosol appears to be efficacious in the treatment of patients with COVID-19. A controlled trial of ribavirin aerosol is ongoing and will provide additional data across a broader patient population.

Efficacy and safety of interferon α-2b spray for herpangina in children: A randomized, controlled trial

ObjectivesThe treatment of acute herpangina is inconsistent. We aim to evaluate the effectiveness and safety of interferon α-2b spray versus Ribavirin for this disease. MethodsA randomized, controlled trial was conducted in eight hospitals in China between 2016 and 2018. 668 patients (1–7 years old) were randomized into an experimental group (treated with Interferon α-2b spray) or control group (received Ribavirin Aerosol). Body temperature returning to normal within 72 h and remaining so for 24 h was the primary outcome; release of oral herpes and adverse events were the secondary outcomes. Results(1) The average age of onset was 2.5 years old. (2) After 72 h treatment, body temperature of 98.5% patients in experimental group and 94.3% in control group returned to normal and remained so for 24 h (P = 0.004). The differences were greater at 48 h treatment (95.2% vs. 85.9%, P < 0.001) and at 24 h (77.5% vs. 66.5%, P = 0.001). (3) The rate of improved oral herpes in the experimental group was higher than that in control group (46.7% vs.37.1%, P = 0.011). No adverse reaction occurred. ConclusionsLocal application of recombinant interferon α-2b spray showed better efficacy for acute herpangina in children. It was safe for use.

Comparison between Watermelon Frost and Ribavirin Aerosol in the Treatment of Oral Herpes in Hand, Foot and Mouth Disease

369 mild HFMD patients were randomly assigned to being treated with either ribavirin or watermelon frost. The course of treatment was 5 days. After this period, the effect of the treatment was evaluated, including the time of disappearance of oral ulcers, fever clearance and vesicles in the hand or foot, together with the clinical grading of the symptoms.

Kangfuxin Liquid combined with conventional treatment for infantile herpetic stomatitis

Objective To evaluate the clinical effect of buccal administration of Kangfuxin Liquid combined with conventional treatment for infantile herpetic stomatitis. Method A total of 103 infantiles with herpetic stomatitis were randomly divided into a Kangfuxin group (51 cases) and a conventional group (52 cases). The conventional group received ribavirin aerosol, and the Kangfuxin group recived buccal administration of Kangfuxin Liquid based on the intervention of convertional group. All children were treated for 5 days. The white blood cell count (WBC) and the serum C-reactive protein (CRP) were determined. Result The total efficiency rate in the Kangfuxin group was significantly higher than that in the conventional group (94.1% vs. 78.8%, χ2=3.895, P<0.05). The healing time of oral ulcers (5.8 ± 1.3 d vs. 7.9 ± 1.5 d, t=10.715), body temperature recovery time (2.1 ± 1.1 d vs. 3.3 ± 1.5 d, t=4.623), and eliminating time of oral mucosal hyperemia and edema (4.3 ± 1.3 d vs. 5.3 ± 1.4 d, t=3.755) in the Kangfuxin group was significantly shorter than those in the conventional treatment group (P<0.01). The WBC (6.5×109 ± 2.2×109/L vs. 9.4×109 ± 2.3×109/L, t=6.537) and serum CRP levels (6.7 ± 1.2 mg/L vs. 9.7 ± 2.5 mg/L, t=12.686) were significantly lower in the Kangfuxin group was significantly lower than those in the conventional treatment group (P<0.01). Conclusions The total efficiency rate of buccal administration of Kangfuxin Liquid combined with conventional treatment for infantile herpetic stomatitis was higher than conventional treatment alone. And the remission time of symptoms of treatment group was shorter. Key words: Stomatitis, herpetic; Child, preschool; Ribavirin; Integrated Chinese traditional and western medicine therapy; Treatment outcome; Kangfuxin Liquid

Therapeutic effect of Kangbingdu oral liquid in combination with ribavirin aerosol for hand, foot, and mouth disease

Objective To evaluate the therapeutic effect of Kangbingdu oral liquid in combination with ribavirin aerosol for hand, foot, and mouth disease （HFMD）. Methods A total of 135 HFMD children were enrolled and assigned to receive ribavirin aerosol alone （ontrol group, 67 patients） or ribavirin aerosol plus Kangbingdu oral liquid group （treatment group, 68 patients） for 7 days. Therapeutic effect was evaluated as the time to fever resolution, subsidence of skin rash and oral ulcers. All throat swab samples were tested using a fluorescence quantitative RT-PCR assay for panenteroviruses, enterovirus 71（EV71）and Coxsackievirus A16 （CA16）. Results The time to fever resolution（2.51±0.42 d vs. 3.92±0.61 d;t=15.621, P<0.01）, subsidence of skin rash（4.22±1.34 d vs. 6.33±1.41 d;t=8.914, P<0.01）and oral ulcers（3.01±0.32 d vs. 4.52±1.21 d;t=9.880, P<0.01）in the treatment group were significantly shorter than those in the control group. The healing rate in the treatment group were significantly higher than that in the control group（88.2%vs. 44.8%;χ^226.761, P<0.01）, and total effective rate was no different in treatment and control groups（94.1%vs. 83.6%;χ^22.801, P=0.094）. The rates of conversion from positive to negative for panenteroviruses（90.9% vs. 52.6%;χ^213.331, P<0.01）and EV71（83.3%vs. 52.4%;χ^24.307, P=0.038）in the treatment group were significantly higher than those in the control group, and the rate of conversion from positive to negative for CA16 was no different in treatment and control groups（93.3%vs. 81.8%;χ^20.082, P=0.774）. Conclusion Kangbingdu oral liquid in combination with ribavirin aerosol may improve the rate of conversion from positive to negative for enteroviruses, reduced the time to fever resolution, subsidence of skin rash and oral ulcers in HFMD children. Key words: Hand,foot and mouth disease; Ribavirin; Kangbingdu oral liquid; Child

Outbreak of Nosocomial Respiratory Syncytial Virus Infections in a Hematology and Transplant Unit.

AbstractAbstract 3032Respiratory syncytial virus (RSV) is a pathogen associated with bronchiolitis in infants and small children. However, immunocompromised adults might also be at risk for severe lower respiratory tract involvement induced by RSV. We report the rapid control of an outbreak of nosocomial RSV infections in an institution with special focus on allogeneic and autologous stem cell transplantations.Between November 2011 and March 2012 56 patients were diagnosed with RSV infection by RT-PCR at our institution. In order to identify possible risk factors for lower respiratory tract involvement in RSV infected patients, clinical course of infection as well as radiological and laboratory findings were evaluated. Characterization of RSV strains in respiratory specimens was achieved by sequence analysis of part of the RSV glycoprotein G gene and phylogenetic comparison of outbreak and community strains was performed.Out of 56 patients with RSV infection, 39 patients showed signs of lower respiratory tract involvement. 14 fatal outcomes were observed. In most of the lethal cases coinfections with other pathogens such as Aspergillus spp. or Pseudomonas aeruginosa were present. Therefore the exact impact of RSV on the fatal outcome remains difficult, if not impossible, to assess. Age, sex, underlying disease, disease control or transplant status did not differ significantly between severe and non-severe cases. However, hypogammaglobulinemia was associated with a higher risk for fatal infection (p = 0.03) in univariate analysis, whereas therapy with oral ribavirin might show a protective effect (p = 0.02). Prolonged viral shedding was frequently observed (median 22.5 [1 – 143] days), most pronounced in patients folllowing allogeneic transplantation (p = 0.04). The major mode of RSV transmission seemed to be direct patient-to-patient contact as suggested by evaluation of patient movements on the wards. Sequence analysis on respiratory specimens obtained from 46 patients revealed the presence of a particular outbreak strain in 40 patients, characterized by an identical nucleotide sequence of RSV GA2 subtype. Phylogenetic analysis showed low prevalence of the outbreak strain in the community. By implementation of rigorous isolation measures containment of outbreak was achieved.Highly contagious viral pathogens such as RSV are able to cause rapidly spreading outbreaks among immunocompromised patients. Hypogammaglobulinemia might be a risk factor for severe lower respiratory tract infection. Treatment with oral ribavirin might have a positive effect on outcome. Rigorous isolation measures are essential to the containment of outbreak. Disclosures:Off Label Use: ribavirin aerosol is FDA approved for severe cases of RSV in infants and young children.

MegaRibavirin aerosol for the treatment of influenza A virus infections in mice

While newer neuraminidase inhibitors have been used recently to treat influenza A and B virus infections, emergence of drug resistance poses potential problems. Previous ribavirin aerosol treatments of influenza were effective and drug resistance was not observed. To make ribavirin aerosol treatment a quicker process and limited to once or twice daily treatments, a MegaRibavirin formulation (100 mg of ribavirin/mL) was developed that when used with the Aerotech II nebulizer was effective in preventing death in a lethal influenza A virus mouse model. Aerosol generated using the Aerotech II nebulizer flowing at 10 L of air/min produced aerosol droplets that contained 2.3 mg of ribavirin/L with a mass median aerodynamic diameter of 1.8 μm. Using this system for treatment, a single daily 30-min exposure on days 1–4 produced a survival rate of greater than 90%. Delaying the start of aerosol treatment for 48 or 72 h and treating once daily for 30 min for two days (days 2–3 and 3–4, respectively) still significantly increased the number of survivors and mean time to death. For the treatment of influenza in general and for pandemic avian influenza, the MegaRibavirin-Aerotech II method of aerosol treatment allows for short treatment periods, minimizes environmental issues and costs less.

Community-acquired respiratory viruses

Community-acquired respiratory viruses

L'emploi d'aérosols de ribavirine lors d'infection à virus respiratoire syncytial est-il justifié ? Évaluation clinique et économique

The controversy about the use of ribavirin aerosol for children at risk (cardiopathy, pneumopathy, premature and immunodeficient patients), in case of respiratory syncytial virus (RSV) infection, led us to stop its prescription in 1993 and study prospectively the patients admitted during the following winters. Criterias of inclusion for this study were those of the Committee on Infectious Diseases of the American Academy of Pediatrics concerning the use of ribavirin aerosol. Two cohorts of patients were studied: the first group included treated patients (ribavirin group: n = 22, ribavirin and support treatment: salbutamol aerosols, respiratory physiotherapy and oxygen-therapy; winters 1989-1990 to 1992-1993); the second group included patients with support treatment only (control group: n = 22; winters 1993-1994 and 1994-1995). The clinical gravity score at admission (4.55 vs 5.23, P = 0.46) and the risk factor scores (3.05 vs 3.27, P = 0.69) of the two groups were identical. Results showed that the children of the ribavirin group stayed much longer in hospital (14.2 vs 8.2 days, P = 0.002) and in the intensive care unit (7.2 vs 0.2 days, P < 0.001) than those of the control group. More support treatment was necessary for the ribavirin group as regard respiratory physiotherapy (3.8 vs 2.7 sessions a day, P = 0.026), the duration of oxygen-therapy (7.3 vs 3.7 days, P = 0.030) and the number of children requiring respiratory assistance (4 vs 0 children, P = 0.116). Administration of ribavirin aerosols (480 US$ a dose) and the way in which such treatment was carried out meant high daily costs for the ribavirin group (1,076 vs 604 US$, P < 0.001). As hospitalization was longer for children treated with ribavirin, the global cost was therefore much higher (15,552 vs 5,156 US$, P < 0.001). The antiviral effect of ribavirin is undeniable. However ribavirin is known to be the cause of severe bronchospasms (two cases in our study) and can also cause moderate and long term bronchospasms, aggravating therefore the clinical evolution of the disease. Our experience shows that administration of ribavirin aerosols in case of RSV infection of inferior respiratory airways seems not to be justified.

Prevention and Treatment of Respiratory Syncytial Virus and Parainfluenza Viruses in Immunocompromised Patients

Immunocompromised patients are vulnerable to severe infections due to respiratory syncytial virus (RSV) and parainfluenza viruses (PIV), and therefore prevention and treatment strategies must be considered. The prevention of RSV disease with high-titer RSV-specific immune globulin has been documented in very young children but has not been systematically studied in high-risk adults. Vaccines against RSV and PIV are under development, but their use in immunocompromised patients is problematic. Ribavirin aerosol therapy is licensed for the treatment of RSV in pediatric patients and has also been used to treat RSV disease in adults and PIV disease in severely immunocompromised children and adults. Uncontrolled trials show that early therapy with ribavirin aerosol may be beneficial, but treatment of pneumonia in patients with respiratory failure is rarely successful. Other potential treatments for RSV or PIV disease include high-dose, short-duration ribavirin therapy; combined immunoglobulin and ribavirin therapy; polyclonal and monoclonal antibodies; and, potentially, immunomodulators.

A paediatric canopy system for aerosol administration and minimized environmental pollution.

A canopy system for ribavirin aerosol administration to infants has been developed in order to improve the control of aerosol treatment, facilitate access to the infant and minimize environmental pollution. The system comprises a transparent canopy, fitted with four sealable apertures. An evacuation flow that is 3 l/min higher than the gas supply was anticipated to prevent aerosol leakage from the canopy. In a clinical evaluation, 10 infants with body weights of 1.8-7.1 kg were placed inside the canopy during 1 hour of simulated treatment. The temperature, relative humidity and carbon dioxide concentration within the canopy were measured repeatedly to study the stability of these variables and their dependence on body weight. Infant body temperature, skin temperature and the respiratory frequency were measured. In a laboratory evaluation, aerosol leakage was studied using an ambient air admixture procedure and smoke tests. The sound level inside the canopy was measured. All physical variables inside the canopy remained stable. The sound level was 52 dBA. The carbon dioxide concentration (1000-3900 PPM) correlated with infant body weight (P < 0.001), as did canopy temperature (25.1-29.6 degrees C, P < 0.05). The relative humidity was 52-88%. Infant body temperatures were not influenced. The respiratory frequency decreased by 13% (P < 0.01). No aerosol leakage was observed. The canopy system facilitates a controlled aerosol therapy with good infant surveillance and accessibility a minimum of environmental pollution and a comfortable physical environment without apparent risks of carbon dioxide rebreathing or cooling stress at body weights of 1.8-7.1 kg.

Use of an in-house-built ribavirin aerosol evacuation system to control incidental employee exposure to ribavirin aerosol.

Ongoing controversy regarding the hazards of exposure of healthcare workers to ribavirin aerosol led to the design and evaluation of a ribavirin aerosol evacuation system that scavenges the excess ribavirin. An oxyhood was placed within a croupette oxygen and cool mist tent. The tent was placed under negative pressure, using the hospital wall suction. Air samples were taken to determine ambient air concentrations and patient exposure concentrations and were compared to airborne ribavirin concentrations that occurred during administration of ribavirin without an evacuation system. The ribavirin evacuation system reduced ribavirin ambient air concentrations from 54 ug/m3 (mean) to 11 ug/m3 (mean) without reducing patient exposure concentrations. The results suggest that the system evaluated is an efficient and inexpensive means of reducing incidental employee exposure to ribavirin aerosol.

Exposures of health-care workers to ribavirin aerosol: a pharmacokinetic study.

We assessed health risks to nurses and therapists exposed occupationally to ribavirin aerosol, a known rodent teratogen, by measuring uptake as a function of exposure concentration. During a 4-d period, healthy, nonsmoking, young adult volunteers (N = 14) were exposed 4 h/d respirable ribavirin aerosol at concentrations that exceeded occupational levels. Intermittent exercise occurred during exposure, and all activities occurred in a simulated hospital room. Ribavirin was assayed in plasma, red cells, and urine; lung function and symptoms were also measured. In 7 volunteers who were exposed to 30 mg/m3 (i.e., received approximately 10% of therapeutic dose), postexposure ribavirin concentrations in plasma and urine were similar on all 4 d, averaging (0.89 mumol/l and 131 mumol/l, respectively. These concentrations decreased after exposure, with half-times of 37-39 h. Red-cell concentrations averaged 31 mumol/l on d 4, accounting for < 5% of inhaled ribavirin mass, and they remained stable for 4 d afterward. In 7 volunteers exposed to 3 mg/m3 (i.e., approximately 1% of therapeutic dose), plasma averaged 0.075 mumol/l and red cells averaged 3 mumol/l on d 4 (i.e., near detection limits). Small variations occurred in lung function, reported symptoms, and hematologic values for exposures to both 3 and 30 microgram/m3; therefore, these effects were most likely not caused by ribavirin. Typical occupational exposures to ribavirin, without recommended protective measures, should result in undetectable or barely detectable body burdens, i.e., approximately 0.1%-1% of levels reported to be toxic to laboratory animals.

High-dose, short-duration ribavirin aerosol therapy compared with standard ribavirin therapy in children with suspected respiratory syncytial virus infection

Children with suspected respiratory syncytial virus infection were examined prospectively in a randomized evaluation of standard ribavirin aerosol therapy (6 gm/300 ml water for 18 hours daily) compared with high-dose, short-duration ribavirin aerosol therapy (6 gm/100 ml water given for a period of 2 hours three times a day) by means of an oxygen hood (n = 20) or a ventilator (n = 12). Viral shedding was quantitated daily; clinical observations were recorded daily by 2 physicians aware and one unaware of treatment assignments. Study characteristics evaluated at entry were not significantly different in the high-dose and the standard-dose groups. Viral titers and clinical scores decreased similarly in both groups during the study; pulmonary function test results were also similar at discharge in children not receiving mechanical ventilation. Potential complications related to aerosol therapy were noted in three patients (one hood patient who was receiving standard therapy; two patients with an endotracheal tube in place who were receiving high-dose therapy); substantial crystallization was noted in the tubing of the patients undergoing intubation and receiving high-dose therapy. Environmental sampling revealed that ribavirin was nearly undetectable near patients supported by mechanical ventilation who were receiving either form of therapy, and was significantly decreased on a daily basis in patients without an endotracheal tube who were receiving high-dose therapy compared with those receiving standard therapy. The effects of high-dose, short-duration aerosol ribavirin therapy were similar to those of standard-dose therapy in our study patients and resulted in a decreased release of ribavirin into the room of patients receiving therapy by means of an oxygen hood. (J P EDIATR 1994;125:635-41)

Aerosolized ribavirin in mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease

To study the effect of ribavirin aerosol therapy on the immediate clinical course of mechanically ventilated children with respiratory syncytial virus lower respiratory tract disease. Prospective, randomized, double-blind, placebo-controlled study. Pediatric intensive care unit (ICU) of a university teaching hospital. Forty-one children requiring mechanical ventilation for respiratory syncytial virus lower respiratory tract disease. Patients were stratified by the presence or absence of and underlying disease and then randomized to receive aerosolized ribavirin (20 mg/mL) or saline for 18 hrs/day for 5 days or until endotracheal extubation, whichever came first. Dependent variables included the time course of the illness and the change in FIO2, ventilatory rate, PaO2/FIO2 ratio, and ventilatory-efficiency index of patients while they received aerosol therapy. Ribavirin- and placebo-treated patient groups were not significantly different in the number of ventilator days (6.4 +/- 6.9 vs. 8.2 +/- 10.1; p = .5), oxygen days (10.8 +/- 7.7 vs. 12.2 +/- 11.8; p = .9), ICU days (7.9 +/- 7.0 vs. 10.3 +/- 11.0; p = .7), or hospital days (12.9 +/- 9.7 vs. 16.2 +/- 14.0; p = .6) after the initiation of aerosol therapy. The change in FIO2, ventilatory rate, PaO2/FIO2 ratio, or ventilatory-efficiency index did not differ between the two groups. No ventilator malfunction was observed. There were six deaths caused by intractable hypoxemia in patients with underlying cardiopulmonary disease. Four of these deaths were in the placebo group and two in the ribavirin group (p = .5). Ribavirin aerosol therapy can be safely administered to mechanically ventilated children with severe respiratory syncytial virus lower respiratory tract disease. However, this therapy does not appear to affect immediate clinical outcome in such patients.

Nature and prevalence of ribavirin aerosol administration in U.S. pediatric hospitals.

A survey was undertaken to determine the nature and prevalence of ribavirin aerosol administration in pediatric hospitals. Ribavirin was administered in 79.4% of the respondents' hospitals. The majority used head hoods for aerosol administration. Ventilators were the primary method used by 6% of the respondents. This study demonstrates typical types of ribavirin exposure and the need to evaluate effects of chronic exposure.