R ESPIRATORY V IRUSES ARE C OMMON ! Coinfection CAP HAP 5% - PDF document

R ESPIRATORY V IRAL I NFECTIONS Infectious Diseases in Clinical Practice February 2020 Jennifer Babik, MD, PhD Associate Clinical Professor Division of Infectious Diseases, UCSF D ISCLOSURES  I have no disclosures.

L EARNING O BJECTIVES By the end of this talk, you will be able to: 1. Recognize the key clinical and radiologic features of influenza and its complications 2. Describe the different diagnostic tests and antiviral options for influenza 1. Recognize the salient features and treatment options for the other common respiratory viruses R OAD M AP  Brief Introduction to Respiratory Viruses  Influenza  Clinical, Diagnosis, Treatment  Quick Takes on other Respiratory Viruses  RSV  Parainfluenza  Human metapneumovirus  Adenovirus  Rhinovirus

R OAD M AP  Brief Introduction to Respiratory Viruses  Influenza  Clinical, Diagnosis, Treatment  Quick Takes on other Respiratory Viruses  RSV  Parainfluenza  Human metapneumovirus  Adenovirus  Rhinovirus  Swine Flu R ESPIRATORY V IRUSES ARE C OMMON ! Coinfection CAP HAP 5% Bacterial 11% Bacterial 23% No No Viral pathogen pathogen 22% Viral 54% 62% 23% Most common viruses isolated (in order): 1. Rhinovirus 2. Influenza, parainfluenza, metapneumovirus, RSV, coronavirus 3. Adenovirus Jain et al, NEJM 2015, 373:415. Shorr et al, Resp Med 2017, 122:76. Micek et al, Chest 2016, 150:1008.

R ESPIRATORY V IRUS S EASONALITY Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Influenza RSV Coronavirus Human Metapneumovirus Adenovirus Rhinovirus Parainfluenza ‐ 3 R OAD M AP  Brief Introduction to Respiratory Viruses  Influenza  Clinical, Diagnosis, Treatment  Quick Takes on other Respiratory Viruses  RSV  Parainfluenza  Human metapneumovirus  Adenovirus  Rhinovirus

I NFLUENZA From the Italian word meaning influence because it was thought the stars and planets caused/controlled disease Fort Riley, Kansas, during the 1918 pandemic A NNUAL B URDEN OF I NFLUENZA $10 billion in Mortality rate Deaths direct medical of ~0.1% costs 12,000 ‐ 61,000 Hospitalizations 140,000 ‐ 810,000 Illnesses 9 million ‐ 45 million CDC, Disease Burden of Influenza, 2020.

I NFLUENZA T YPES Influenza A Influenza B  Multiple subtypes (e.g. H1N1)  No subtypes  Reassortment  drastic  No reassortment (b/c few change in H +/ ‐ N  pandemic related viruses in animals)  Currently circulating:  ~25% of circulating influenza but wide annual variation  Seasonal H1N1  Seasonal H3N2  Pandemic H1N1 Influenza A and B are clinically indistinguishable Su et al, Clin Infect Dis 2014, 59:252. Glezen, Clin Infect Dis 2014, 59:1525. 2019 ‐ 20 S EASON : M IX OF V IRUSES S O F AR pandemic H1N1 (influenza A) Influenza B https://www.cdc.gov/flu/weekly/index.htm

S EASONAL VS P ANDEMIC I NFLUENZA Hospitalized patients with pandemic H1N1 are more likely to be: Demographics Complications  Need ICU admission  Younger  Need intubation  Obese  Have PNA, septic shock  Pregnant  Have higher mortality?  Have no comorbidities (conflicting results) Lee et al, J Infect Dis 2011, 203:1739. Reed et al, Clin Infect Dis 2014, 59:166. H OW B AD IS F LU S EASON T HIS Y EAR (H OSPITALIZATIONS )? 10,000 deaths so far (average) 2019 ‐ 20 https://www.cdc.gov/flu/weekly/index.htm

N EW IDSA G UIDELINES FOR I NFLUENZA Uyeki et al, Clin Infect Dis 2018. C ASE #1 96 year old woman with COPD is admitted in March with 1 day of SOB, wheeze. No fevers or myalgias. She had the flu vaccine, and her son has a URI.  Afebrile, HR 125, BP 90/60. WBC 11, lactate 6.  What is your suspicion for influenza given lack of fever?

H OW C OMMON IS F EVER IN I NFLUENZA IN THE E LDERLY ? 1. 10% 2. 35% 3. 60% 4. 90% C LINICAL M ANIFESTATIONS OF I NFLUENZA Headache Congestion/rhinorrhea Sore throat/hoarseness Altered mental status (encephalopathy, encephalitis) Nonproductive cough Chest pain (myocarditis, pericarditis) Abdominal pain Vomiting, diarrhea Myalgia (rhabdo, myositis) Weakness Fever Chills Malaise/fatigue Uyeki et al, Clin Infect Dis 2018.

M AKING A C LINICAL D IAGNOSIS IS H ARD !  Abrupt onset of fever + cough is >70% sensitive for flu but signs/sx of flu are variable in different populations All Elderly Immunocompromised Fever 75% 35% 35 ‐ 70% Cough 90% 70% 50 ‐ 90%  In the ER/inpatient setting, the sensitivity of a provider’s clinical diagnosis for flu is only ~30 ‐ 35% Kumar et al, Clin Infect Dis 2018, 67:9 Call et al, JAMA 2005; 293:987. Apewokin et al, OFID 2014. Dugas et al, Am J Emerg Med 2015, 33:770. Miller et al, J Infect Dis 2015, 212:1604. B UT S HE G OT THE V ACCINE !  Vaccine effectiveness usually 40 ‐ 50%, varies based on predominant subtype  Influenza B 54%  Seasonal H1N1 67%  Pandemic H1N1 61%  H3N2 33% (good match), 23% (poor match)  CDC/IDSA: a history of vaccination should not be used in decision ‐ making about diagnostics or empiric Rx CDC, Seasonal Influenza Vaccine Effectiveness, 2005 ‐ 2017. Belongia et al, Lancet ID 2016, 16:942. Uyeki et al, Clin Infect Dis 2018.

C ASE #1 C ONTINUED  Rapid influenza PCR positive for influenza A H3N2  Is this severe influenza pneumonia or does she have a bacterial co ‐ infection?  Afebrile, HR 125, BP 90/60  WBC 11, lactate 6 T HIS P ATIENT ’ S S EPSIS IS M OST L IKELY R ELATED T O : 1. Primary influenza pneumonia 2. Secondary bacterial pneumonia 3. Could be either

P RIMARY I NFLUENZA P NEUMONIA  Occurs in ~40% of those Key Point hospitalized with influenza • Presentation indistinguishable from bacterial superinfection  A severe illness! • No difference in  20% present with sepsis symptoms, CXR, labs  10% present with shock  50% admitted to the ICU  40% require mechanical ventilation  25% develop ARDS  20% mortality Jain et al, Clin Infect Dis 2012, 54:1221. Rice et al, Crit Care Med 2012, 40:1487. P RIMARY I NFLUENZA PNA: R ADIOLOGY  Infiltrates bilateral 60 ‐ 70%, unilateral 30 ‐ 40%  Consolidations in 75 ‐ 90%  Interstitial thickening 60% Consolidations + GGO Centrilobular nodules + GGO GGO predominant Jain et al, Clin Infect Dis 2012, 54:1221. Jartti et al, Acta Radiologica 2011, 52: 297. Jain et al, N Engl J Med 2009, 361:1935. Agarwal et al, AJR 2009, 193: 1488. Kang et al, J Comput Assist Tomogr 2012, 36:285

S ECONDARY B ACTERIAL P NEUMONIA  Likely responsible for most of the deaths from the 1918 pandemic  How common is it now?  <3% of all cases of influenza  10% of all inpatients  20 ‐ 30% of critically ill or deaths MMWR 2009, 58:1. Jain et al, CID 2012, 54:1221. Jain et al, NEJM 2009, 361:1935. Rice et al, Crit Care Med 2012, 40:1487. Morens et al, J Infect Dis 2008; 198:962. S ECONDARY B ACTERIAL P NEUMONIA : E TIOLOGY  Predominantly colonizers of the nasopharynx:  S. pneumoniae ~40 ‐ 50%  S. aureus ~30 ‐ 40% (  in critically ill)  Group A Streptococcus 5 ‐ 25%  Others:  H. influenzae , other GNRs  Atypicals : Mycoplasma , Legionella Chertow and Memoli, JAMA 2013, 309:275. MMWR 2009, 58:1. Jain et al, Clin Infect Dis 2012, 54:1221. Jain et al, N Engl J Med 2009, 361:1935. Rice et al, Crit Care Med 2012, 40:1487.

S ECONDARY B ACTERIAL P NEUMONIA : P RESENTATION  Classic:  Period of improvement  recurrence of symptoms 4 ‐ 7 days later  Reality:  Present on ~day 5 of illness without a period of improvement  Presentation indistinguishable from severe influenza pneumonia (no difference in symptoms, CXR, labs) So how can I tell the difference between influenza PNA and bacterial PNA? MMWR 2009, 58:1. Jain et al, CID 2012, 54:1221. Jain et al, NEJM 2009, 361:1935. Rice et al, Crit Care Med 2012, 40:1487. W HAT D O THE N EW IDSA G UIDELINES S AY ?  Work ‐ up and empirically treat bacterial coinfection in patients with suspected/confirmed influenza who:  Initially present with severe disease  Deteriorate after initial improvement, particularly in those treated with antivirals  Fail to improve after 3 ‐ 5 days of antiviral therapy (consider) Uyeki et al, Clin Infect Dis 2018.

W HAT A BOUT P ROCALCITONIN ?  Multiple RCTs, Cochrane review 2017 of PCT use in LRTI:  ~2.5 day reduction in Abx   Abx side effects   mortality (8.6 vs 10.0%)  ProACT study (RCT of 1664 patients, NEJM 2018):  No difference in Abx use, adverse effects  ?due to low baseline Abx use in the study  Discrimination between viral vs. bacterial infection/coinfection (cut ‐ off 0.25): Sensitivity 70 ‐ 90%, NPV 80 ‐ 90% Bottom line: PCT may be a useful adjunct but should not replace clinical suspicion Schuets et al, JAMA 2009, 302:1059. Pfister et al, Crit Care 2014, 18:R44. Rodriguez et al, J Infect 2016, 72:143. Self et al, Clin Infect Dis 2017, 65:183. Schuetz et al, Cochrane Database Syst Rev 2017. Huang et al, NEJM 2018, 379:236. N EW IDSA CAP G UIDELINES : U SE OF P ROCALCITONIN Rationale Should PCT be Recommendation • Many of the PCT used to decide if studies looked at CAP it is safe to NO, if a patient vs URI (not viral vs has confirmed withhold empiric bacterial CAP) CAP you should antibiotics in a start antibiotics • No PCT cut ‐ off can patient with CAP irrespective of the sufficiently distinguish (i.e., can it PCT result viral vs bacterial (cut ‐ distinguish viral vs (strong rec, off of ≥ 0.1, PCT only bacterial CAP)? moderate quality of ~80% sensitive for evidence) bacteria) Metlay et al, AJRCCM 2019, 200:e45. Self et al, Clin Infect Dis 2018.