Q&A: The importance of antiviral use for influenza in the ED

The CDC estimates that in recent years, seasonal influenza has killed between 12,000 (2011-2012 season) and 56,000 (2012-2013 season) people in the United States annually. In the current influenza season, influenza activity in the U.S. has reached epidemic proportions.

“Influenza leads to a quarter of a million ER visits every year,” Frank LoVecchio, DO, MPH, FACEP, vice chairman of the department of emergency medicine at Maricopa Medical Center, told Infectious Disease News. “People say it’s ‘just the flu,’ but it’s hard to find any disease that is costlier to our society.”

Despite the significant health threat posed by influenza, in addition to the cost in terms of hospital stays and lost productivity, the use of antiviral medications for influenza continues to be low.

Infectious Disease News spoke with LoVecchio about possible reasons for underuse of antivirals, long-held misconceptions about these medications, and the potential benefits of antiviral use in the ED. – by Jennifer Byrne

Can you discuss the role of antivirals in decreasing influenza-related morbidity and mortality?

I’m a big believer in antivirals. I’ve been practicing emergency medicine and critical care medicine, and now my work has evolved into infectious disease research. I’ve been practicing for more than 2 decades, and there are very few things that we do as clinicians that can improve your outcome by a quarter.

The antiviral peramivir, which is known as Rapivab [Seqirus], has been shown to do that. If a patient’s symptoms were going to last for 4 days, it can knock it down to 3 days. If they’re going to have a fever for 40 hours, it can knock about 12 hours off that, or about 25%. That doesn’t happen with antibiotics, not with pneumonia or other diseases.

CDC researchers have reported that only 7.5% of patients who present to ambulatory care for acute respiratory illness received an antiviral prescription, and of those with confirmed influenza, only 15% were prescribed antivirals. Why do you think these rates are so low, and what can be done to improve antiviral prescribing in the U.S.?

That’s a great question. Probably, I’d say lack of awareness is the number one factor, along with familiarity with other drugs such as antibiotics. Some of them might feel that antivirals don’t work well. Yet we continue to overprescribe antibiotics, and I can tell you that there are tons of doctors who will just give an antibiotic for the flu. It doesn’t do anything, it’s costly, and it leads to resistance. But they know if they want to keep the patient, or the patient is just going to go down the road to another physician, they should prescribe something. We give antibiotics because we’ve made patients have that expectation.

It’s very hard to change physician behavior. On average, it takes about 5 to 7 years for physicians to adopt something new.

Maybe some physicians aren’t up to date with the CDC guidelines, or with the Infectious Diseases Society of America guidelines. To be honest, I think once you get out there into practice, you may lose the impetus to read as much and to follow these guidelines.

I think we need to educate physicians and increase compliance with the guidelines — not guidelines that I made up, but guidelines that the CDC made up.

Five years ago, we might have had this conversation about why clinicians don’t treat sepsis more aggressively. But now, with sepsis, the government is involved; they’re sending us guidelines requiring that we treat sepsis in a timely fashion. Patients with sepsis must get a fluid bolus, for example. If not, you’re going to get in trouble, you’re going to get dinged, and you’re potentially going to lose money. That’s what causes us to pay a little bit more attention.

Can you discuss the current guidelines for antiviral use in the ED?

Well, most of them are adapted from what we see from the CDC. The CDC says if you’re mildly sick, you’re going to go home to treat [the illness], especially if it’s 1 to 2 days of symptoms. But if in the higher risk groups, such as kids, the elderly, diabetics, patients with neurological disorders, or immunosuppressed patients, you should consider treating with antivirals in the hospital, even if it’s greater than 2 days of symptoms.

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So, when a patient presents to the emergency department with flu-like symptoms, you have a couple of options. One is inhalational medication, which we don’t really use because the patient has to take a puffer twice a day, and the patient can’t have upper respiratory infections, asthma or COPD, and they can’t have milk allergies, so it doesn’t make much sense. So, we’re essentially stuck between Tamiflu [oseltamivir, Roche] and Rapivab. With Rapivab, the advantage is you give an IV; it’s one and done, and it lasts for 5 days or so.

That’s a significant advantage with peramivir; when the patient walks out of your emergency department, they’re therapeutic. Whereas with the oral agent, you have to give one tablet twice daily for 5 days, or 10 total doses, and it’s been well-studied that less than half of patients are compliant with that regimen.

Additionally, the oral regimen assumes the patient’s digestive system is intact; that they’re not vomiting and can keep oral medication down. With the 15-minute IV infusion, it doesn’t matter.

Are there any specific hospital policies that could make ED clinician testing more consistent?

We’ve implemented a system where we ask patients a lot of questions in triage, and one of the things we’ve implemented is asking people [about] signs and symptoms of the flu. If you test positive on this questionnaire, we usually test you for the flu.

Some hospitals check everyone for the flu when they get admitted, and I think that’s not a bad idea. Pediatric hospitals often check for respiratory syncytial virus, because they don’t want you to spread your illness to everyone else. We know that with influenza, a patient can be asymptomatic for a day or two, and longer if they’re immunosuppressed, and can still be giving it to other patients and be contagious. So, some hospitals have implemented policies, but it’s certainly not mandated.

In my opinion, testing patients for the flu makes sense, and could save some money. If you know someone has tested positive for the flu, you might not need lots of other labs and chest X-rays and bloodwork. You might just be able to give them an antiviral.

What can be done to better manage patients at risk for influenza hospitalization?

Number one, we’ve got to get them all vaccinated. We encourage everyone to run, not walk, to get the flu shot if they haven’t already, but no flu shot has ever been 100% effective. Number two, patients who are sick have got to have common sense. They’ve got to wash their hands and cover their faces when they sneeze or cough. And the third thing is, if you do think a patient has influenza and they are part of a high-risk population, there is good data from the CDC that antivirals decrease mortality. In patients who are relatively benign, where they just have the flu and are over 18, they’re going to go home. Maybe they’re just a little bit dehydrated. But in kids, people over age 65, diabetics, Native Americans, obese patients, immunosuppressed patients and those with neurological conditions, antiviral treatment has been shown to save lives.

Would there be any potential down-side to prescribing antivirals? Is there potential for resistance?

The short answer is there is very, very little downside. Some data have come out suggesting that patients are temporarily a bit loopy on [antivirals], but for me, that’s very confusing in the sense that we can’t know whether that happened because of the drug or because of the fever. The downside really is just the cost., However, if I had the flu and there was a way to make my disease last 3 days instead of 4, I’d want that treatment. I’d be reducing cost by being able to get back to work; a day is worth it to me.

In terms of resistance, there is very little of that. I don’t know of any resistance to peramivir, for example. That doesn’t mean there isn’t going to be any: Influenza A and B mutate really quickly. There’s a little bit of resistance to Tamiflu, but there is very little resistance so far.

I think it’s fair to say that we’re not at the point of overuse; we’re at the point of significant underuse. You had cited earlier that in outpatient settings, only 7.5% of patients received these medications. So, it’s not to the point of causing resistance. We’ll have to have that conversation in a couple of years.

References:

Havers F, et al. Clin Infect Dis. 2014;doi:10.1093/cid/ciu422.

Mueller MR, et al. Ann Emerg Med. 2010;doi:10.1016/j.annemergmed.2009.09.019.

For more information:

Frank LoVecchio, DO, MPH, can be reached at 925 East McDowell Road, 3rd Floor, Phoenix, Ariz. 85006; email: rossie@ruderfinn.com.

Disclosure: LoVecchio reports serving as a spokesperson for peramivir.