key: cord-0994789-6j4sdvj6
authors: Stiver, H Grant; Evans, Gerald A; Aoki, Fred Y; Allen, Upton D; Laverdière, Michel
title: Guidance on the use of antiviral drugs for influenza in acute care facilities in Canada, 2014–2015
date: 2015
journal: Can J Infect Dis Med Microbiol
DOI: nan
sha: 67c79979c388cfcad87bb12d0ea644699500d736
doc_id: 994789
cord_uid: 6j4sdvj6

This article represents the second update to the AMMI Canada Guidelines document on the use of antiviral drugs for influenza. The article aims to inform health care professionals of the increased risk for influenza in long-term care facilities due to a documented mismatch between the components chosen for this season’s vaccine and currently circulating influenza strains. Adjusted recommendations for the use of antiviral drugs for influenza in the acute care setting for this season are provided.

Clinical trials with the neuraminidase inhibitors (NIs) oseltamivir and zanamivir and and meta-analyses of oseltamivir therapy administered within 36 h to 48 h of symptom onset to low-risk outpatients with influenza (where placebo-controlled trials were ethically safe) have shown that overall, these agents shorten the duration of symptoms by 1 to 1.5 days (1) (2) (3) (4) . Systematic reviews of studies investigating the efficacy of NIs in treating mild to moderate influenza illness in outpatients have not adequately addressed the significantly greater benefit of NI treatment in very ill hospitalized patients, nor the greater benefit of earlier treatment after onset of symptoms (4) . Earlier therapy with oral oseltamivir administered within 12 h of symptom onset was shown to reduce symptoms by 3.6 days (5) . Inhaled zanamivir shortened the duration of major influenza symptoms by 3 days compared with placebo in individuals who were febrile at enrollment and received zanamivir within 30 h (3) . In low-risk outpatients, NI treatment of mild influenza illness may be considered but is optional (6) .

On the other hand, observational cohort-controlled studies of patients with severe influenza due to the H3N2 subtype and H1N1 pandemic subtype treated in hospital with oseltamivir clearly demonstrate reduction in mortality, and this benefit was still observed if oseltamivir was started up to 4 to 5 days after the onset of symptoms (7, 8) . The majority of these patients usually had pre-existing risk factors for severe influenza, but approximately 30% were healthy younger persons with no discernable risk factors.

In the current 2014-2015 influenza season, A(H3N2) influenza has accounted for the majority of influenza cases documented by testing. In addition, a significant antigenic drift has occurred in the majority of H3N2 influenza strains obtained from ill patients, resulting in a clinically relevant mismatch between the predominant circulating H3N2 influenza virus and the H3N2 vaccine strain. The WHO Global Influenza Surveillance and Response System laboratories have tested >96,535 specimens: 23,421 were positive for influenza viruses, of which 22,129 (94.5%) were typed as influenza A and 1292 (5.5%) as influenza B. Of the subtyped influenza A viruses, 163 (1.7%) were influenza A (H1N1) pdm09, and 9211 (98.3%) were influenza A (H3N2) (9) .

Although the vaccine may still provide partial protection, it is not expected to be optimal. Therefore, vaccinated individuals may present to acute care facilities with influenza-like illness (ILI) and require treatment with NI.

To date, the majority of the predominating H3N2 virus isolates of influenza are susceptible to oseltamivir and zanamivir. All isolates of H1N1 are oseltamivir-and zanamivir-susceptible. Almost all isolates of influenza B are also susceptible to oseltamivir and zanamivir.

With ili to An Acute cAre fAcility?

During peaks of influenza activity in the community, a case definition in older children and adults of fever >38 °C with cough has a positive predictive value of 86% and a negative predictive value of 39.3% for influenza in patients attending an outpatient clinic (10) . Of course, these values vary depending on the prevalence of influenza in the community relative to other respiratory infections. In older patients with chronic obstructive pulmonary disease, who have been vaccinated for influenza, only the presence of fever >37.8° and myalgias correlated with influenza, but with a lower positive predictive value of 41% (11) . Other respiratory viruses, including but not limited to: respiratory syncytial virus (RSV), adenovirus, parainfluenza, rhinovirus, coronavirus or human metapneumovirus infection, may account for those with non-influenza infection. The use of influenza polymerase chain reaction (PCR) is preferred to direct fluorescent antigen detection (DFA) due to its greater sensitivity. A nasopharyngeal swab is preferred for influenza PCR testing, particularly if the patient requires hospital admission. If the patient is intubated, an endotracheal aspirate can be substituted for an NP swab. If an NP swab has been performed and is negative, and the patient is subsequently intubated, an Table 2 . Oseltamivir oral suspension may also be used by adult patients who cannot swallow a capsule. If oseltamivir oral suspension is not available, oseltamivir capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup. For children old enough to safely swallow capsules, the 30 mg and 45 mg capsules can also be taken as outlined in Table 1 .

Patients with severe immunodeficiency, and very ill patients on ventilators may not improve and continue to shed influenza viruses for 

A detailed discussion of the appropriate antibiotic management of patients with suspected bacterial pneumonia is beyond the scope of this document. However, if a patient presents with an acute respiratory infection on a background of an influenza outbreak, and a chest radiograph demonstrates pulmonary infiltrates, primary influenza or secondary bacterial pneumonia, or both, are possibilities. Primary influenza pneumonia typically presents with severe shortness of breath and occurs within one to three days of initial symptom onset (12) . Clinicians should be aware that the presentation of a biphasic illness with reappearance of fever after defervesence from a typical influenza illness might represent a complicating secondary bacterial pneumonia. Bacterial pneumonia should be strongly suspected when a typical influenza illness is resolving, usually around the fifth day, and then there is a recurrence of fever and productive cough, often but not always with purulent sputum. In severely ill patients, appropriate antibiotics for community-acquired or nursing home-acquired pneumonia should be instituted immediately, as well as NI antiviral drug treatment, pending an etiologic diagnosis.

A detailed discussion of the appropriate infection control measures for the management of patients with suspected influenza is beyond the scope of this document. However, the following measures are generally employed.

During an influenza outbreak, all individuals with ILI admitted to the emergency department or the hospital should be placed on Droplet and Contact precautions pending the results of testing on the NP swab. 

Post-exposure prophylaxis: Secondary cases of influenza in family members of an index case can be reduced by early institution of post-exposure prophylactic oseltamivir or zanamivir (16) . Hospitalized patients and HCW, regardless of their vaccine status, who have had unprotected close contact with a patient with ILI, may be offered either oseltamivir at a dose of 75 mg once daily or zanamivir inhalation, two puffs (10 mg) once daily for seven (oseltamivir) to 10 (zanamivir) days to reduce the chance of influenza illness. This is especially important this influenza season in the face of the vaccine mismatch. Post-exposure prophylaxis is less likely to be effective if started >48 h after the exposure. In high-risk patients, the use of postexposure prophylaxis, even >48 h, may be justified. In HCWs and lowrisk hospitalized patients identified >48 h after exposure, observation and early treatment if symptoms arise is the preferred strategy.

Close observation and early treatment is recommended for individuals who choose not to receive post-exposure antiviral prophylaxis.

Pre-exposure prophylaxis with either oseltamivir or zanamivir for hospitalized patients or staff is not routinely recommended. This recommendation differs from that for residents and staff in long-term or chronic care facilities. Pre-exposure prophylaxis for patients may be considered in specific circumstances (eg, in high-risk semi-closed hospital units such as transplant units) when at least one laboratoryconfirmed case occurs on a hospital unit. The end of a unit outbreak is generally considered when no new cases of ILI have appeared for ≥7 days after the onset of the last case. Pre-exposure prophylaxis increases the risk of long-term use, and the development of resistance. 

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