What are the most effective prevention and treatment strategies for respiratory tract infections in transplant and other immunocompromised patients?
Michael Boeckh, MD, Fred Hutchinson Cancer Research Center, Seattle, WA, reviewed and compared prophylaxis, pre-emptive approaches, and treatment of respiratory syncytial virus (RSV) and influenza in transplant recipients during his presentation at the 48th annual meeting of the IDSA in Vancouver.
Boeckh said that “one way to risk stratify people is to determine the presence of lymphopenia, and this has been shown in several cohorts.” Importantly, the presence of lymphopenia can predict progression to lower respiratory tract infection (LRTI), and therefore facilitate pre-emptive therapy. "I think the most commonly used approach at the moment is pre-emptive during the early stage of the infection," he said.
Currently, there are two strategies for intervention at the stage of upper respiratory tract infection (URTIs) that are being used in transplant centers. One is to give an antiviral drug, or oral/IV RBV, or RSV-IG/PVZMAB, regardless of lymphopenia. "This has been shown to have an effect, though some centers restrict this approach to lymphopenia of less than 300 m/L," Boeckh said. By comparison, the strategies for LRTIs are limited to aerosolized RBV and RSV-IG/PLVZMAB, or oral/IV RSV plus RSV-IG/PLVZMAB.
With respect to antibody-based therapies, palivizumab prophylaxis in high risk infants has been shown effective. And data from a phase I study show it to efficacious in hematopoietic stem cell transplantation (HSCT) recipients. Data from animal models also show efficacy for polyclonal RSV-IG and palivizumab in RSV infection and immunosuppression.
These current treatment approaches appear to be effective. Data on RSV outbreaks from 1997 and 2007 from the Fred Hutchinson Cancer Research Center show a significant reduction in the number of RSV-related deaths in 2007 compared with 1997, 23% vs. 8% respectively. This is likely attributable to several factors including more outpatient management, a more aggressive approach to infection control, differences in management such as improved diagnostics for RSV (PCR), and earlier treatment of LRTI. The use of chest x-rays and CT scans for defining disease likely also play a role as does the use of palivizumab for LRTI specifically.
Like RSV, influenza is also associated with morbidity and mortality in immunosuppressed patients. In terms of pre-emptive treatment, a study of Oseltamivir for URTI in HCT patients recently demonstrated significant efficacy in preventing URTI. And there was a significant trend in improved survival. Data on the timing of treatment showed significant benefit for initiating treatment within 24 hours following diagnosis. However, there was still an effect, with borderline significance, for starting treatment after 48 hours.
Data on the initiation of Oseltamivir treatment for H5N1 initiated between 0-8 days also show a significant benefit compared with treatment initiation after eight days.
In terms of steroids, there is a paucity of data. However, Boeckh and colleagues recently completed an analysis which showed that corticosteroids (<1mg/kg day or beclomethasone dipropionate or > 1mg/kg day) in the HSCT setting didn't appear to have an adverse impact. "Patients can probably remain on their current dose. Whether or not it should be increased is a question that should be tested. But there didn't appear to be an urgent need to decrease the dose," Boeckh said.