Let’s be honest – respiratory virus season is not a physician’s favorite time of the year.   In fact, if you take away the presents and holiday cheer sometimes it feels as though all you are left with is runny noses, sore throats and sinus pressure.  All those visiting relatives?  They may bring along “la gripa” – my personal favorite term for the flu (influenza).

Influenza is a major pathogen and leads to significant morbidity and mortality in the US.  Patients with risk factors, such as chronic lung disease, diabetes or heart disease, are at risk for more complications.  Among cancer patients, transplant recipients and other immunocompromised hosts, the burden can be even more pronounced, leading to pneumonia, ICU admission, intubation and even death.  At the same time, unlike the other RNA-viruses of winter (e.g. RSV, metapneumovirus), we have methods to prevent (influenza vaccine) and treatment (oseltamivir).  Besides the obvious – “Get your Flu shot” diatribe (and you should get you flu shot ASAP if you haven’t because #vaccineswork [ref]), there are data that treatment of influenza with neuraminidase inhibitors like oseltamivir is critical for patients with weakened immunity.

flu
Influenza A virions (from Public Health Image Library at the CDC)

A colleague on Twitter (Michael Calderwood @CalderwoodMD) pointed out an advanced access paper that was recent added to Open Forum Infectious Diseases on oseltamivir use (paper link).  The data is from the Drs. Oboho/Jain and colleagues, and addresses the use of oseltamivir in patients with community acquired pneumonia (CAP).  This paper comes from a larger parent study, EPIC (Etiology of Pneumonia in the Community) Study (adult study and peds study).  They went back to the data to evaluate patients admitted to the hospital during October 1 – April 30 – i.e. Influenza season.

In this sub-study the authors sought to better understand reasons for oseltamivir use among patients admitted with CAP among over 2500 patients in the trial.  When addressing clinical risk factors for use of oseltamivir, I was somewhat surprised to see that among patients with chronic health conditions,  immunosuppression was not associated with a statistical increase in oseltamivir use (unadjusted OR 1.01 [95% CI 0.69-1.47]).  This is small subset of the population and immunosuppression has broad range of meanings in clinical practice, but this issue is important.  It reflects my personal experience – oseltamivir isn’t always given to symptomatic high-risk patients even when levels in the community are high.  In some studies even high-risk hematologic and solid cancer patients with proven influenza don’t always receive oseltamivir. (ref)

Oseltamivir has been shown to be most beneficial if given early in the first 48 hours of illness (ref and ref), suggesting that most immunosuppressed patients in this study should have received empiric therapy.   Why then are providers gun-shy about starting treatment in these high-risk patients?  One guess is that national CAP guidelines (ref) providers pay more attention to empiric antibiotics – and when they see pneumonia they focus on bacterial causes and not viral etiologies.  It is also possible, that oseltamivir’s cost (~$150 US for a course) makes others avoid empiric use to wait for diagnostic results.  In immunocompromised hosts, it may be that providers focus on antibacterial agents  in those with pneumonia to avoid the possibility of impending sepsis.  I also wonder if the increased use of PCR testing for respiratory viruses, which may be more pronounced in high-risk patients, allowed many clinicians to avoid treatment with a negative test.

Still, these data suggest a need to further assess this situation.  As an advocate of thoughtful and appropriate antibiotic use, I worry in this situation that delays in oseltamivir/zanamivir may have negative effects on high-risk patients.  It is critical to assure adequate testing in immunocompromised patients for respiratory viruses, but we need to improve upon efforts to enhance empiric therapy for these patients with new upper and lower respiratory virus symptoms during influenza season.  Waiting for results may not be appropriate, and since many locations still do not have PCR availability – waiting for diagnostic results may dangerous.  Infectious disease, hematology/oncology and transplant teams should take time to work with primary care clinics and ERs to promote early/empiric oseltamivir/zanamivir use in high-risk patients, as it is these locations where such patients may present first.

Finally, I suppose it never hurts to make a final plug, to get high-risk patients and their close contacts vaccinated for infuenza.  What could be a better holiday treat for patients then avoiding the need for treatment altogether?

Reference:  Oboho IK, et al. Oseltamivir use among children and adults hospitalized with community-acquired pneumonia. Open Forum Infectious Diseases (epub December 2016)

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