Download Respiratory syncytial virus infection: Treatment Authors: Frederick E

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Ebola virus disease wikipedia , lookup

Cryptosporidiosis wikipedia , lookup

Orthohantavirus wikipedia , lookup

Schistosomiasis wikipedia , lookup

HIV wikipedia , lookup

Pandemic wikipedia , lookup

Norovirus wikipedia , lookup

West Nile fever wikipedia , lookup

Oesophagostomum wikipedia , lookup

Dirofilaria immitis wikipedia , lookup

Chickenpox wikipedia , lookup

Marburg virus disease wikipedia , lookup

Coccidioidomycosis wikipedia , lookup

Herpes simplex virus wikipedia , lookup

Human cytomegalovirus wikipedia , lookup

Hepatitis C wikipedia , lookup

Antiviral drug wikipedia , lookup

Hospital-acquired infection wikipedia , lookup

Hepatitis B wikipedia , lookup

Henipavirus wikipedia , lookup

Neonatal infection wikipedia , lookup

Lymphocytic choriomeningitis wikipedia , lookup

Middle East respiratory syndrome wikipedia , lookup

Transcript
Respiratory syncytial virus infection: Treatment
Authors:
Frederick E Barr, MD
Barney S Graham, MD, PhD
Section Editors:
Morven S Edwards, MD
George B Mallory, MD
Deputy Editor:
Mary M Torchia, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Nov 2016. | This topic last updated: Jul 28, 2015.
INTRODUCTION — Respiratory syncytial virus (RSV) causes acute respiratory tract illness in
persons of all ages. Almost all children are infected by two years of age, and reinfection is
common [1]. The clinical manifestations vary with age, health status, and whether the infection
is primary or secondary.
The treatment of respiratory syncytial virus infection in infants, children, and adults will be
discussed here. The epidemiology, microbiology, clinical manifestations, diagnosis, and
prevention of RSV infection are discussed separately. (See "Respiratory syncytial virus
infection: Clinical features and diagnosis" and "Respiratory syncytial virus infection:
Prevention".)
OVERVIEW — The discussion that follows assumes that the patient's illness is severe enough
to require hospital admission or to pursue an etiologic diagnosis since specific etiologic
diagnosis is usually not sought in otherwise healthy patients with mild respiratory tract infections
who are treated symptomatically as outpatients. (See "Respiratory syncytial virus infection:
Clinical features and diagnosis", section on 'Diagnosis'.)
Indications for hospitalization in children with bronchiolitis are discussed separately.
(See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on
'Indications for hospitalization'.)
Outpatient treatment for patients with upper respiratory tract infections, bronchiolitis, or
pneumonia who do not have a specific microbiologic diagnosis are discussed separately.
(See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Empiric
therapy' and "The common cold in children: Management and prevention" and "Bronchiolitis in
infants and children: Treatment; outcome; and prevention", section on 'Nonsevere bronchiolitis'.)
Therapy for RSV infection of the lower respiratory tract is primarily supportive. Inhaled
bronchodilators are not routinely recommended for infants and young children with bronchiolitis,
but a one-time trial may be warranted for those with severe disease (eg, nasal flaring;
retractions; grunting; respiratory rate >70 breaths per minute; dyspnea; or cyanosis).
(See "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on
'Bronchodilators'.)
Antiviral agents are available, but their use is not indicated in most patients. More aggressive
therapy, including immunotherapy, or antiviral and immunotherapy with or without
corticosteroids may be warranted for immunocompromised patients, as described below.
(See 'Ribavirin' below and 'Passive immunotherapy' below and 'Combination therapy' below.)
SUPPORTIVE CARE — Supportive care for children with RSV lower respiratory tract infection
(LRTI) may include hospitalization and fluid and respiratory support. The supportive care and
inpatient treatment for bronchiolitis and pneumonia are discussed in detail separately. Important
aspects of care and those specific to children with RSV will be summarized below.
(See "Pneumonia in children: Inpatient treatment", section on 'Supportive
care' and "Bronchiolitis in infants and children: Treatment; outcome; and prevention", section on
'Severe bronchiolitis'.)
Respiratory support — Infants with RSV bronchiolitis and pneumonia frequently have arterial
oxygen saturations of ≤90 percent. Infants whose oxygen saturation is consistently ≤90 percent
should be treated with supplemental oxygen. (See "Continuous oxygen delivery systems for
infants, children, and adults".)
Mechanical ventilation may be required in patients with severe respiratory
symptoms and/or apnea due to RSV. The frequency of mechanical ventilation varies according
to age and underlying health status from approximately 5 percent in infants hospitalized with
RSV to up to 50 percent of adults with leukemia and myelosuppression [2-6].
PHARMACOTHERAPY
Bronchodilators — We do not routinely suggest inhaled bronchodilators for children with RSV
bronchiolitis. Meta-analyses of randomized trials and systematic reviews suggest that
bronchodilators may provide modest short-term clinical improvement, but do not affect overall
outcome, may have adverse effects, and increase the cost of care [7-10]. (See "Bronchiolitis in
infants and children: Treatment; outcome; and prevention", section on 'Bronchodilators'.)
Corticosteroids — We recommend against the use of corticosteroids in infants and young
children (<24 months) with RSV bronchiolitis or pneumonia. In older children and adults,
corticosteroids may be beneficial in the management of RSV-associated bronchial reactivity,
particularly in those with asthma, in whom RSV reinfection may have triggered an exacerbation.
(See "Acute asthma exacerbations in children: Emergency department management".)
Corticosteroids have the potential to decrease bronchiolar swelling and airway obstruction
through their antiinflammatory effects. However, in randomized trials [11,12], meta-analyses
[13], and systematic reviews [14,15], they have not been shown to be beneficial for the
treatment of bronchiolitis. Data are limited on the use of corticosteroids in patients with
bronchiolitis who require mechanical ventilation.
The use of corticosteroids in the treatment of bronchiolitis in children is discussed in detail
separately. (See"Bronchiolitis in infants and children: Treatment; outcome; and prevention",
section on 'Glucocorticoids'.)
Ongoing studies are evaluating the value of corticosteroid therapy in combination with passively
administered antiviral immunoglobulin, particularly in immune-compromised patients, as
discussed below. (See 'Combination therapy' below.)
Bronchodilators plus corticosteroids — Combination therapy with bronchodilators and
corticosteroids in infants with bronchiolitis is discussed separately. (See "Bronchiolitis in infants
and children: Treatment; outcome; and prevention", section on 'Glucocorticoids'.)
Hypertonic saline — The use of hypertonic saline in the treatment of RSV bronchiolitis in
children is discussed separately. (See "Bronchiolitis in infants and children: Treatment;
outcome; and prevention", section on 'Nebulized hypertonic saline'.)
Ribavirin — Ribavirin is a nucleoside analog with good in vitro activity against RSV. Ribavirin is
approved by the US Food and Drug Administration (FDA) for the treatment of RSV infection.
In children — The routine use of nebulized ribavirin in infants and children with RSV lower
respiratory tract infection (LRTI) is not recommended. The efficacy of ribavirin in this population
has not been clearly proven [16,17]. In addition, ribavirin is expensive and must be given early
in the course to be effective, and there are concerns regarding occupational exposure [16].
(See 'Adverse effects' below.)
Randomized controlled trials comparing ribavirin with placebo in children with RSV LRTI have
yielded mixed results. Some studies have demonstrated decreased severity of illness,
decreased duration of mechanical ventilation, oxygen therapy and hospital stay, and decreased
viral shedding [18-21], whereas other studies have not demonstrated these benefits [22-24]. A
2004 systematic review of randomized trials comparing ribavirin with placebo in infants and
children with RSV infection and LRTI found that trials of ribavirin lack sufficient power to provide
reliable estimates of the effects [16].
The American Academy of Pediatrics (AAP) recommends against the routine use
of ribavirin [25]. Ribavirin should be reserved for immunosuppressed patients with severe RSV
infection. Consultation with an expert in infectious diseases is recommended before its use.
In adults — Although the routine use of ribavirin is not recommended for infants and children
with RSV LRTI, ribavirin may be beneficial for certain adults. Early use of inhaled ribavirin has
been shown to reduce morbidity and mortality in adult hematopoietic cell transplant recipients
who develop RSV infections [26,27]. In small case series, oral ribavirin has been used to
successfully treat RSV upper and lower respiratory tract disease in adult hematopoietic cell
transplant recipients [28,29]. The efficacy of ribavirin for patients with solid-organ transplants is
unknown [30,31].
Contraindications — Ribavirin is considered to be contraindicated in pregnant women, and a
negative pregnancy test should precede its use in women of child-bearing age. (See 'Pregnant
women' below.)
The prescribing information for oral ribavirin recommends that ribavirin be avoided in men
whose partners are pregnant [32]. Given the long half-life of ribavirin, it is also recommended
that women who receive ribavirin and the female partners of men who receive ribavirin avoid
pregnancy for six months after completion of treatment.
Adverse effects — Adverse effects related to occupational exposure to ribavirin have not been
reported. However, the National Institute of Occupational Safety and Health has published
recommendations to reduce the ambient air concentrations of ribavirin and limit occupational
exposure to hospital personnel [33].
Passive immunotherapy — In a 2006 systematic review, neither intravenous immunoglobulin
with a high neutralizing activity against RSV (RSVIG) nor monoclonal antibody proved beneficial
in the treatment of RSV in hospitalized infants and young children [34]. RSVIG is no longer
available.
A pilot study of treatment with RSVIG demonstrated decreased viral shedding and improvement
in oxygenation in children with RSV LRTI [35]. However, subsequent randomized studies found
no benefit in reducing hospital stay, intensive care unit stay, mechanical ventilation, or the need
for supplemental oxygen [36,37]. Similarly, a study using an RSV-specific humanized
monoclonal antibody (palivizumab) also found no benefit when used as therapy (rather than
prophylaxis, which is discussed separately) [38]. (See "Respiratory syncytial virus infection:
Prevention", section on 'Palivizumab'.)
Additional monoclonal antibodies against RSV are being studied, but have no current clinical
applications [39-41].
Combination therapy
Ribavirin and immunotherapy — Combined antiviral therapy and immunotherapy may be
warranted in severely ill immunocompromised patients with RSV LRTI [42].
Adult hematopoietic cell transplant patients with RSV pneumonia have a high risk of mortality
(approximately 70 percent) [43]. In these patients, uncontrolled studies suggest that
combination therapy with ribavirin and intravenous immunoglobulin is associated with improved
survival [44-48]. Additional studies in RSV-infected lung transplant recipients have suggested
that combined ribavirin (nebulized or intravenous) with intravenous
immunoglobulin and/or corticosteroids can reduce mortality, length of mechanical ventilation,
and incidence of bronchiolitis obliterans [49].
Although combined ribavirin and intravenous immunoglobulin has not been supported by a
randomized trial, this expensive treatment is now sometimes used in selected patients.
Similarly, the combination of intravenous immunoglobulin and palivizumab is sometimes used in
severely ill immunocompromised patients but has not been well studied.
Ribavirin and corticosteroids — We suggest ribavirin in combination with passive
immunotherapy and/orcorticosteroids for immune-compromised adults with severe RSV LRTI.
Combined treatment with intravenous ribavirin and oral corticosteroids in an uncontrolled study
of 18 adult lung transplant recipients was well tolerated and cleared RSV infection by
immunofluorescent antibody testing. There was no mortality, and only one patient developed
bronchiolitis obliterans [50].
PREGNANT WOMEN — The management of pregnant women with RSV is similar to that for
other adults (see'Overview' above), except that ribavirin is avoided because studies in rodents
(rats, rabbits, hamsters) demonstrated teratogenicity and/or embryolethality [51]. The risk in
human pregnancy is uncertain due to the small number of reported exposures, but preliminary
findings from a ribavirin pregnancy registry have not suggested human teratogenicity [52]. Birth
defects occurred in 3 of 49 live births with direct maternal exposures and 3 of 69 live births
following indirect exposure via the male sexual partner, with no consistent pattern of
abnormality.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials,
"The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain
language, at the 5th to 6th grade reading level, and they answer the four or five key questions a
patient might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics patient
education pieces are longer, more sophisticated, and more detailed. These articles are written
at the 10th to 12th grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Bronchiolitis (and RSV) in infants and
children (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Therapy for respiratory syncytial virus (RSV) infection of the lower respiratory tract is
primarily supportive. Supportive care may include hospitalization and fluid and respiratory
support. (See 'Supportive care'above.)
●We suggest that inhaled bronchodilators not be used routinely for children with RSV
bronchiolitis (Grade 2B). (See 'Bronchodilators' above.)
●We recommend not using corticosteroids in infants and young children (<24 months) with
RSV bronchiolitis or pneumonia (Grade 1A). However, corticosteroids may be beneficial in
the management of lower airway obstruction in older children and adults.
(See 'Corticosteroids' above.)
●We recommend not using ribavirin routinely in the management of infants and children
with RSV lower respiratory tract infection (LRTI) (Grade 1B). (See 'Ribavirin' above.)
●We suggest ribavirin in combination with passive immunotherapy and/or corticosteroids
for immune-compromised adults with severe RSV LRTI (Grade 2C). (See 'Ribavirin' above
and 'Combination therapy'above.)
●Neither intravenous immunoglobulin with a high neutralizing activity against RSV nor
monoclonal antibody has as yet proven beneficial in the treatment of RSV in hospitalized
infants and young children. (See'Passive immunotherapy' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1.
Committee on Infectious Diseases. From the American Academy of Pediatrics: Policy
statements--Modified recommendations for use of palivizumab for prevention of respiratory
syncytial virus infections. Pediatrics 2009; 124:1694.
2.
Wald TG, Miller BA, Shult P, et al. Can respiratory syncytial virus and influenza A be
distinguished clinically in institutionalized older persons? J Am Geriatr Soc 1995; 43:170.
3.
Henderson FW, Collier AM, Clyde WA Jr, Denny FW. Respiratory-syncytial-virus
infections, reinfections and immunity. A prospective, longitudinal study in young children. N Engl
J Med 1979; 300:530.
4.
Whimbey E, Couch RB, Englund JA, et al. Respiratory syncytial virus pneumonia in
hospitalized adult patients with leukemia. Clin Infect Dis 1995; 21:376.
5.
Seo S, Campbell AP, Xie H, et al. Outcome of respiratory syncytial virus lower
respiratory tract disease in hematopoietic cell transplant recipients receiving aerosolized
ribavirin: significance of stem cell source and oxygen requirement. Biol Blood Marrow
Transplant 2013; 19:589.
6.
Renaud C, Xie H, Seo S, et al. Mortality rates of human metapneumovirus and
respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation
recipients. Biol Blood Marrow Transplant 2013; 19:1220.
7.
Hartling L, Bialy LM, Vandermeer B, et al. Epinephrine for bronchiolitis. Cochrane
Database Syst Rev 2011; :CD003123.
8.
Hartling L, Fernandes RM, Bialy L, et al. Steroids and bronchodilators for acute
bronchiolitis in the first two years of life: systematic review and meta-analysis. BMJ 2011;
342:d1714.
9.
Skjerven HO, Hunderi JO, Brügmann-Pieper SK, et al. Racemic adrenaline and
inhalation strategies in acute bronchiolitis. N Engl J Med 2013; 368:2286.
10.
Gadomski AM, Scribani MB. Bronchodilators for bronchiolitis. Cochrane Database Syst
Rev 2014; :CD001266.
11.
Cade A, Brownlee KG, Conway SP, et al. Randomised placebo controlled trial of
nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis. Arch Dis Child 2000;
82:126.
12.
van Woensel JB, Vyas H, STAR Trial Group. Dexamethasone in children mechanically
ventilated for lower respiratory tract infection caused by respiratory syncytial virus: a
randomized controlled trial. Crit Care Med 2011; 39:1779.
13.
Patel H, Platt R, Lozano JM, Wang EE. Glucocorticoids for acute viral bronchiolitis in
infants and young children. Cochrane Database Syst Rev 2004; :CD004878.
14.
Lozano JM. Bronchiolitis. Clin Evid 2004; :370.
15.
King VJ, Viswanathan M, Bordley WC, et al. Pharmacologic treatment of bronchiolitis in
infants and children: a systematic review. Arch Pediatr Adolesc Med 2004; 158:127.
16.
Ventre K, Randolph A. Ribavirin for respiratory syncytial virus infection of the lower
respiratory tract in infants and young children. Cochrane Database Syst Rev 2004; :CD000181.
17.
Ottolini MG, Hemming VG. Prevention and treatment recommendations for respiratory
syncytial virus infection. Background and clinical experience 40 years after discovery. Drugs
1997; 54:867.
18.
Hall CB, McBride JT, Walsh EE, et al. Aerosolized ribavirin treatment of infants with
respiratory syncytial viral infection. A randomized double-blind study. N Engl J Med 1983;
308:1443.
19.
Taber LH, Knight V, Gilbert BE, et al. Ribavirin aerosol treatment of bronchiolitis
associated with respiratory syncytial virus infection in infants. Pediatrics 1983; 72:613.
20.
Rodriguez WJ, Kim HW, Brandt CD, et al. Aerosolized ribavirin in the treatment of
patients with respiratory syncytial virus disease. Pediatr Infect Dis J 1987; 6:159.
21.
Smith DW, Frankel LR, Mathers LH, et al. A controlled trial of aerosolized ribavirin in
infants receiving mechanical ventilation for severe respiratory syncytial virus infection. N Engl J
Med 1991; 325:24.
22.
Meert KL, Sarnaik AP, Gelmini MJ, Lieh-Lai MW. Aerosolized ribavirin in mechanically
ventilated children with respiratory syncytial virus lower respiratory tract disease: a prospective,
double-blind, randomized trial. Crit Care Med 1994; 22:566.
23.
Moler FW, Steinhart CM, Ohmit SE, Stidham GL. Effectiveness of ribavirin in otherwise
well infants with respiratory syncytial virus-associated respiratory failure. Pediatric Critical Study
Group. J Pediatr 1996; 128:422.
24.
Guerguerian AM, Gauthier M, Lebel MH, et al. Ribavirin in ventilated respiratory
syncytial virus bronchiolitis. A randomized, placebo-controlled trial. Am J Respir Crit Care Med
1999; 160:829.
25.
American Academy of Pediatrics. Respiratory syncytial virus. In: Red Book: 2015 Report
of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long
SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.667.
26.
McColl MD, Corser RB, Bremner J, Chopra R. Respiratory syncytial virus infection in
adult BMT recipients: effective therapy with short duration nebulised ribavirin. Bone Marrow
Transplant 1998; 21:423.
27.
Waghmare A, Campbell AP, Xie H, et al. Respiratory syncytial virus lower respiratory
disease in hematopoietic cell transplant recipients: viral RNA detection in blood, antiviral
treatment, and clinical outcomes. Clin Infect Dis 2013; 57:1731.
28.
Casey J, Morris K, Narayana M, et al. Oral ribavirin for treatment of respiratory syncitial
virus and parainfluenza 3 virus infections post allogeneic haematopoietic stem cell
transplantation. Bone Marrow Transplant 2013; 48:1558.
29.
Gueller S, Duenzinger U, Wolf T, et al. Successful systemic high-dose ribavirin treatment
of respiratory syncytial virus-induced infections occurring pre-engraftment in allogeneic
hematopoietic stem cell transplant recipients. Transpl Infect Dis 2013; 15:435.
30.
Krinzman S, Basgoz N, Kradin R, et al. Respiratory syncytial virus-associated infections
in adult recipients of solid organ transplants. J Heart Lung Transplant 1998; 17:202.
31.
Doud JR, Hinkamp T, Garrity ER Jr. Respiratory syncytial virus pneumonia in a lung
transplant recipient: case report. J Heart Lung Transplant 1992; 11:77.
32.
Rebetol (ribivarin) www.merck.com/product/usa/pi_circulars/r/rebetol/rebetol_pi.pdf
(Accessed on December 19, 2013).
33.
Hospital investigations: Health Hazards. In: OSHA Technical Manual (OTM). US
Department of Labor; Occupational Safety and Health Administration, Washington, DC 1999.
34.
Fuller H, Del Mar C. Immunoglobulin treatment for respiratory syncytial virus infection.
Cochrane Database Syst Rev 2006; :CD004883.
35.
Hemming VG, Rodriguez W, Kim HW, et al. Intravenous immunoglobulin treatment of
respiratory syncytial virus infections in infants and young children. Antimicrob Agents
Chemother 1987; 31:1882.
36.
Rodriguez WJ, Gruber WC, Welliver RC, et al. Respiratory syncytial virus (RSV) immune
globulin intravenous therapy for RSV lower respiratory tract infection in infants and young
children at high risk for severe RSV infections: Respiratory Syncytial Virus Immune Globulin
Study Group. Pediatrics 1997; 99:454.
37.
Rodriguez WJ, Gruber WC, Groothuis JR, et al. Respiratory syncytial virus immune
globulin treatment of RSV lower respiratory tract infection in previously healthy children.
Pediatrics 1997; 100:937.
38.
Sáez-Llorens X, Moreno MT, Ramilo O, et al. Safety and pharmacokinetics of
palivizumab therapy in children hospitalized with respiratory syncytial virus infection. Pediatr
Infect Dis J 2004; 23:707.
39.
Corti D, Bianchi S, Vanzetta F, et al. Cross-neutralization of four paramyxoviruses by a
human monoclonal antibody. Nature 2013; 501:439.
40.
McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer bound
to a prefusion-specific neutralizing antibody. Science 2013; 340:1113.
41.
Boyoglu-Barnum S, Gaston KA, Todd SO, et al. A respiratory syncytial virus (RSV) antiG protein F(ab')2 monoclonal antibody suppresses mucous production and breathing effort in
RSV rA2-line19F-infected BALB/c mice. J Virol 2013; 87:10955.
42.
Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev
2000; 13:371.
43.
Hertz MI, Englund JA, Snover D, et al. Respiratory syncytial virus-induced acute lung
injury in adult patients with bone marrow transplants: a clinical approach and review of the
literature. Medicine (Baltimore) 1989; 68:269.
44.
Whimbey E, Champlin RE, Englund JA, et al. Combination therapy with aerosolized
ribavirin and intravenous immunoglobulin for respiratory syncytial virus disease in adult bone
marrow transplant recipients. Bone Marrow Transplant 1995; 16:393.
45.
Ghosh S, Champlin RE, Englund J, et al. Respiratory syncytial virus upper respiratory
tract illnesses in adult blood and marrow transplant recipients: combination therapy with
aerosolized ribavirin and intravenous immunoglobulin. Bone Marrow Transplant 2000; 25:751.
46.
DeVincenzo JP, Hirsch RL, Fuentes RJ, Top FH Jr. Respiratory syncytial virus immune
globulin treatment of lower respiratory tract infection in pediatric patients undergoing bone
marrow transplantation - a compassionate use experience. Bone Marrow Transplant 2000;
25:161.
47.
De Vincenzo JP, Leombruno D, Soiffer RJ, Siber GR. Immunotherapy of respiratory
syncytial virus pneumonia following bone marrow transplantation. Bone Marrow Transplant
1996; 17:1051.
48.
Flynn JD, Akers WS, Jones M, et al. Treatment of respiratory syncytial virus pneumonia
in a lung transplant recipient: case report and review of the literature. Pharmacotherapy 2004;
24:932.
49.
Schmidt AC, Johnson TR, Openshaw PJ, et al. Respiratory syncytial virus and other
pneumoviruses: a review of the international symposium--RSV 2003. Virus Res 2004; 106:1.
50.
Glanville AR, Scott AI, Morton JM, et al. Intravenous ribavirin is a safe and cost-effective
treatment for respiratory syncytial virus infection after lung transplantation. J Heart Lung
Transplant 2005; 24:2114.
51.
Reprotox. Ribavirin. www.reprotox.org/Members/AgentDetail.aspx?a=1334 (Accessed
on December 19, 2013).
52.
Roberts SS, Miller RK, Jones JK, et al. The Ribavirin Pregnancy Registry: Findings after
5 years of enrollment, 2003-2009. Birth Defects Res A Clin Mol Teratol 2010; 88:551.