Intravenous ribavirin is a safe and cost-effective treatment for respiratory syncytial virus infection after lung transplantation.
BACKGROUND
Community-acquired viral infections, such as respiratory syncytial virus (RSV), represent a risk factor for bronchiolitis obliterans syndrome (BOS), the major limiting factor for long-term survival after lung transplantation (LTx). RSV often presents with acute bronchiolitis and may be fatal in 10% to 20% of patients. Standard therapies for RSV include nebulized ribavirin with or without steroids, but are costly and inconvenient. We investigated the utility of intravenous (IV) ribavirin with steroids for the treatment of RSV infection after LTx.


METHODS
RSV was identified in nasopharyngeal and throat swabs (NPS) using indirect fluorescent antibody (IFA) testing in 18 symptomatic patients, which was confirmed by viral culture in 14. Data were collected for the period between April 2002 and October 2004. The study included 10 men and 8 women, mean age 42 +/- 15 (range 18 to 63) years. Transplant procedures were 5 single LTx and 13 bilateral LTx. RSV diagnosis was made on Day 1,374 +/- 1,270 (range 61 to 4,598, median 935) post-operatively. Underlying diagnoses included cystic fibrosis (n = 9), emphysema (n = 7) and pulmonary fibrosis (n = 2). All 18 patients received intravenous (IV) ribavirin (33 mg/kg on Day 1 and 20 mg/kg/day thereafter in 3 divided doses) with oral prednisolone (1 mg/kg) until repeat NPS were negative for RSV on IFA. Median therapy was 8 days (6 to 15).


RESULTS
The mortality rate was 0%. Mean FEV1 fell from 2.1 +/- 1.0 liter (0.7 to 3.7 liters) to 1.8 +/- 0.9 liter (0.5 to 3.6 liters) (p < 0.001), but recovered to 2.1 +/- 0.9 (0.7 to 3.7 liters) within 3 months and was maintained at follow-up of 521 +/- 328 days (141 to 1,023 days, median 302). Only 1 patient developed bronchiolitis obliterans syndrome (BOS). Complications included mild hemolytic anemia (blood hemoglobin fell from 122 +/- 22 [84 to 154] g/liter to 107 +/- 18 [75 to 138] g/liter, p = 0.02). Cost savings per 8-day course were $US15,913 when compared with nebulized therapy at 6 g/day (p < 0.001).


CONCLUSIONS
This is the largest reported series of treated RSV cases after LTx and the first to show that therapy with IV ribavirin and oral corticosteroids is well tolerated and effective. Cost utility vs nebulized therapy has been established. Early diagnosis and management are essential to prevent airway epithelial injury and subsequent BOS.
Glanville
Allan R
AR
Lung Transplant Unit, St. Vincent's Hospital, Sydney, Australia. aglanville@stvincents.com.au
Scott
Andrew I R
AI
Morton
Judith M
JM
Aboyoun
Christina L
CL
Plit
Marshall L
ML
Carter
Ian W
IW
Malouf
Monique A
MA
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007262:Infusions, Intravenous; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy* / Q000191:economics / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000191:economics* / Q000209:etiology; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D012254:Ribavirin