COMMENTARY

Commonly Encountered Respiratory Virus Infections: Update and New Treatments

Shmuel Shoham, MD; Megan K. Morales, MD

Disclosures

November 08, 2016

Specific Antiviral Agents for Influenza Infection

Neuraminidase inhibitors. Oseltamivir, zanamivir, and peramivir are the most widely used treatments for influenza A and B.

For pregnant women, experience is greatest with oseltamivir (Tamiflu®), which is the drug of choice provided that there is not widespread resistance in the yearly circulating strains. It is administered orally for an average duration of 5 days, although in severely ill patients and immunocompromised patients, treatment is often longer. Courses as long as 12 weeks can be well tolerated when given as reduced-dose prophylaxis.[38]

Treatment with neuraminidase inhibitors, such as oseltamivir, is associated with earlier resolution of illness, earlier return to normal activities, and reduced duration of fever.[39] In addition, treatment with oseltamivir leads to fewer influenza-related complications, including LRTIs, antibiotic use, and hospitalizations.[40] When used as prophylaxis (75 mg once daily), oseltamivir decreases the incidence of influenza by up to 92%, reduces shedding of virus, and reduces complications of influenza (bronchitis, sinusitis, and pneumonia), while not preventing a protective antibody response or leading to the development of resistance.[38] Nausea, vomiting, and diarrhea are the most commonly experienced side effects of oseltamivir.[38,41] The first generic version of oseltamivir was approved by the FDA in August 2016.

Zanamavir (Relenza®) is a powder inhaled through a disk inhaler. It is not recommended for use in patients with chronic lung disease or those allergic to lactose, an ingredient in the powder. Nausea and diarrhea, the most common side effects, occurred at rates similar in the treatment and placebo groups.

Peramivir (Rapivab®) is the most recently approved neuraminidase inhibitor. It has a higher binding affinity to neuraminidase than oseltamivir, is administered as one to five intramuscular or intravenous doses, and requires dose adjustment for renal dysfunction.[42] Like the other neuraminidase inhibitors, diarrhea is the main side effect, although serious skin and hypersensitivity reactions have also been reported rarely.

Favipiravir (Avigan®), developed as T-705, is a broad-spectrum antiviral with activity against a range of pathogens, including Ebola, West Nile virus, norovirus, RSV, rhinovirus, poliovirus, yellow fever virus, and influenza.[43,44,45,46] The drug metabolite selectively inhibits influenza virus RNA polymerase without causing toxicity to mammalian cells.[44] In animal models, it has decreased death, viral burden, and symptoms, even sometimes when initiated 5-7 days after infection.[44] It inhibits strains that are resistant to current antiviral therapies and has a synergistic effect with both oseltamivir and peramivir.[43,45]

Later this fall, a poster on S-033447/S-033188, a novel inhibitor of influenza A and B, is scheduled to be presented at the annual Infectious Diseases Society of America meeting. S-033188 inhibits the initiation of messenger RNA synthesis, the first viral proliferation step after entry into the cell. The company behind the drug expects it to be a single-dose therapy and more effective than neuraminidase inhibitors. They additionally reported that a phase 2 study was under way in Japan as of February 2016, and the product may reach market by March 2018.

Amantadine and rimantadine. The first antiviral treatments for influenza were the adamantane derivatives amantadine and rimantadine. These are active only against influenza A; influenza B lacks the M2 protein upon which the drug acts. These drugs have fallen out of use owing to their low barrier to development of resistance. Global resistance to the neuraminidase inhibitors in recent years has ranged from approximately 0.5% to 2%.[47]

Symptomatic relief in pregnant patients may also include acetaminophen. Nonpregnant patients without other contraindications may use aspirin or ibuprofen for fever and aches.

Providers should be aware of the possibility of secondary bacterial pneumonia after a course of influenza. If the patient presents with a second worsening or a seeming relapse, they should be evaluated for bacterial pneumonia, commonly due to streptococci or Staphylococcus aureus.

A happy ending. The patient is admitted to the hospital, is treated with oseltamivir and supportive care, and improves. She is discharged from hospital after 48 hours. The rest of her pregnancy is uneventful, and she ultimately delivers a healthy full-term infant.

Advice for Practicing Clinicians

Common respiratory viral infections, such as RSV, PIV, and influenza, cause a spectrum of illnesses that range from nuisance "colds and flus" to more serious lower respiratory tract disease. Increased awareness of the impact that respiratory viral infections can have on an individual patient, the healthcare system, and society as a whole have rendered the phrase "it's just a viral infection" something of a relic.

Diagnostic innovations are identifying patients with such infections, and the ongoing development of multiple antiviral drugs with diverse mechanisms of action will hopefully help us meet the challenges posed by respiratory viral infection.

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