ECHO-Antibiotic Stewardship Program: Influenza Basics - November 19, 2015 Charles Krasner, M.D. UNSOM

ECHO- Antibiotic Stewardship Program:
 Influenza Basics

November 19, 2015
Charles Krasner, M.D.
UNSOM
Sierra NV Veterans Affairs Hospital

Flu still quiet …

Yearly peaks for influenza like illness clinic visits

Respiratory/influenza mortality rates

What was wrong with the 2014 flu vaccine- poor match up with what
occurred
     In 2009- major antigenic shift occurred - major change in viral structure with the
      appearance of Swine Flu (H1N1) No pre-existing immunity in the community
      (except in the old ). Lead to major epidemic that winter, many deaths.
     In 2014-minor antigenic drift developed- minor change in viral structure
      occurred. This virus was referred to as the H3N2v (variant).
      In situations like in 2014, there may be some cross immunity to the new virus from
    prior exposure or vaccination in the community. H3N2v first noted in 3/2014, but
    not commonly isolated in the country till September,2104 - too late for companies
    to produce updated vaccines- poor match resulted. Fortunately not a severe
    influenza year despite this mismatch.

What is in the 2015 flu vaccines

 All of the 2015-2016 influenza vaccine is made to protect against the following three
  viruses:
 •an A/California/7/2009 (H1N1)pdm09-like virus
 •an A/Switzerland/9715293/2013 (H3N2)-like virus
 •a B/Phuket/3073/2013-like virus. (This is a B/Yamagata lineage virus)

 Some of the 2015-2016 flu vaccine is quadrivalent vaccine and also protects against
  an additional B virus (B/Brisbane/60/2008-like virus). This is a B/Victoria lineage virus.
 Vaccines that give protection against three viruses (2As and 1B) are called trivalent
  vaccines. Vaccines that give protection against four viruses (2As and 2Bs) are called
  quadrivalent vaccines.

How flu vaccines are made

 Egg based Flu vaccines- over 70 years most common way. CDC grows the
  viruses or in eggs, then provides them to manufacturers that inject them
  into fertilized hens eggs- incubated – then harvested – either inactivated
  (killed) for flu shots, Or attenuated live viruses used in nasal spray
 Cell based Flu vaccines- since 2012. CDC egg grown viruses are grown
  next in cultured mammalian cells and the fluid is removed and viral
  antigens purified. Less eggs required, quicker manufacturing period
 Recombinant Flu vaccines- since 2013. Does not require chicken eggs,
  antibiotics, etc at all. Influenza HA protein - which induces immune
  response in people, is combined with another partial virus and grown in the
  lab. Only 100% egg free vaccine

Types of Flu vaccines
 Fluzone Trivalent Vaccine (IM)– egg based, contain two A viruses and one B virus
  (>6 months)
 Fluzone Quadrivalent- (IM) egg based, contain two A viruses and two B viruses
  (>6 months)
 Fluzone High-Dose Vaccine- (IM Trivalent) - has more 4x more antigen to
  stimulate immune response, indicated for >64 years. The trade off is this year it is
  only a trivalent vaccine, next year will be quadrivalent. 2014 NEJM study showed
  25 % reduction in illness in seniors compared to standard trivalent vaccine
 Fluzone Intradermal Quadrivalent- very tiny needle !!!(age 18 to 64 years).
  Available at Target pharmacies
 FluMist Quadrivalent – (intra-nasal spray) egg based, attenuated live virus for
  healthy, non-pregnant people age 2-49.
 Flublok -Trivalent Recombinant Infl. Vaccine (RIV3) for egg allergic > 18 years.
  Available at Target Pharmacies .covered by insurance

If it’s on the internet it must be true

Usual excuses…

 Has mercury in it and causes autism. No thimerosal in single dose syringes.
  Thimerosal is quickly eliminated in the urine, unlike mercury.
 The Flu vaccine gave me the flu- all vaccines except FluMist are killed virus. The
  FluMist virus is attenuated and can not live at body temperature, no
  documented case of person to person transmission.
 I am healthy and don’t need it! – typical excuse of HCWs, however you have
  an ethical responsibility to your patients and co-workers who are not healthy to
  not give them the flu
 I cannot take the vaccine because I am pregnant/live with an
  immunocompromised patient- these are some of the people most at risk for
  getting influenza complications
 I am a pediatric brain surgeon and so I must know all about the dangers of
  vaccines

CDC definition of “influenza-like” case during an outbreak.
Fever critical to differentiate from the common cold which is also
prevalent now. Rapid screen is helpful only if positive, negative go by
clinical evaluation, known ongoing flu outbreak.

  Fever > 101.5F° (38.6°C) plus ONE of the following:

 1. cough
 2. Sore throat
 3. headache
 4. myalgias

Healthy people who are not that sick probably do not need treatment.

The CDC states the following high risk groups should take antivirals,
particularly if ill for less than 48 hours. Do not wait for the result of diagnostic
tests, and remember rapid tests miss many cases:

 •any flu patient sick enough to be hospitalized
 •those with a severe, complicated, or progressive health problem
  such as COPD including asthma, diabetes, heart disease or a
  suppressed immune system
 •children younger than 2
 •adults 65 or older
 •pregnant women
 •American Indians or Alaska Natives
 •those who are morbidly obese (a body-mass index of 40 or higher)
 •residents of nursing homes and assisted-care facilities

Influenza Anti-viral medication-
 both remain active all circulating strains of Influenza A

Prescribing Tamiflu

 If taken within 48 hours of symptom onset, reduce duration of illness by
  about one to two days
 Can cause headache, nausea and vomiting
 There is no resistance to Tamiflu in any of the influenza strains seen this year
 ***If patient fits the CDC influenza-like case definition (and is at increased
  risk for complications) start treatment without waiting for test results
 Standard dose is 75mg BID for 5 days (kids and renal patients are dosed
  differently)
 Expensive – out of pocket cost can be as much as $140 (GoodRx.com) for 5
  day supply

US Influenza Seasonal Forecast-10.21.15

 US Influenza Forecast 2015-6 Season. Jim Wilson, M.D.

Influenza case presentation

 33 year old female – comorbidities: asthma/smoking hx, severe obesity.
 No flu vaccine this year
 48 hours before admit : has muscle aches, fever- Goes to urgent care -
  screen is positive for influenza A. Given Tamiflu . Takes one dose – is
  confused, hallucinating, laying in bed- family calls pharmacist- told to stop,
  possible side-effect of Tamiflu
 Day of admit: paramedics called, taken to ER- in septic shock , intubated,
  transferred to Renown ICU

CASE, cont -pg. 2

Clinical presentation at Renown             CXR - pneumonia seen
    Systolic blood pressure in the 80’s,
     on fluids and pressor agents
    Labs: AST/ALT- 1500/3000
    INR- 1.5x normal
    Creatinine- 1.6mg/dl
    Placed on empiric ceftriaxone,
     azithromycin, linezolid plus Tamiflu

Case, cont- pg. 3

 Microbiology:
     Blood cultures- negative
      Bronchoscopy: Methicillin Resistant Staph Aureus (MRSA)
 Diagnosis: Influenza A infection complicated by pneumonia and MRSA
  Toxic Shock Syndrome – a toxin mediated process characterized by shock
  plus multi-organ failure
 Patient had prolonged ICU course but eventually recovered and went
  home after period of rehabilitation.