10/15/2018 R ESPIRATORY V IRAL I NFECTIONS IN H OSPITAL M EDICINE Management of the Hospitalized Patient October 2018 Jennifer Babik, MD, PhD Associate Clinical Professor Division of Infectious Diseases University of California, San Francisco D ISCLOSURES I have no disclosures. 1
10/15/2018 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 Rapid ‐ Fire Respiratory Viruses RSV Parainfluenza Human metapneumovirus Adenovirus Rhinovirus Swine Flu 2
10/15/2018 R OAD M AP Brief Introduction to Respiratory Viruses Influenza Clinical, Diagnosis, Treatment Rapid ‐ Fire 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 Viral pathogen No 22% Viral 54% pathogen 23% 62% 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. 3
10/15/2018 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 Other Respiratory Viruses RSV Parainfluenza Human metapneumovirus Adenovirus Rhinovirus Swine Flu 4
10/15/2018 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 Deaths direct medical costs 12,000 ‐ 80,000 Hospitalizations 140,000 ‐ 710,000 Illnesses 9 million ‐ 36 million CDC, Disease Burden of Influenza, May 2018. 5
10/15/2018 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% 6
10/15/2018 D OES T HIS P ATIENT H AVE I NFLUENZA ? All patients Patients >60 years old Sensitivity Specificity Sensitivity Specificity Fever 75% 50% 35% 90% Cough 90% 20% 70% 70% Fever and cough 65% 65% 30% 95% Key point: Fever, fever and cough are less sensitive but more specific in patients >60 years old Other symptoms? Myalgia, chills, headache, sore throat, congestion were not sensitive or specific Call et al, JAMA 2005; 293:987. M AKING A C LINICAL D IAGNOSIS IS H ARD ! In the ER/inpatient setting, the sensitivity of a provider’s clinical diagnosis for flu is only ~30 ‐ 35% Dugas et al, Am J Emerg Med 2015, 33:770. Miller et al, J Infect Dis 2015, 212:1604. 7
10/15/2018 I NFLUENZA IN I MMUNOCOMPROMISED H OSTS Classic symptoms less likely Shedding (median days) 9 More likely to have: 8 Need for hospitalization 7 Need for intubation 6 Higher mortality 5 4 Longer viral shedding: 3 Median 8 vs 5 days 2 1 But 15% of ICH patients can shed 0 for prolonged periods (>30 days) ICH non ‐ ICH Memoli et al, Clin Infect Dis 2014, 58:214. Ison, Influenza and Other Respir Viruses 2013, 7 Suppl 3: 60. 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: Do not use in decisions re: diagnosis or empiric treatment CDC, Seasonal Influenza Vaccine Effectiveness, 2005 ‐ 2017. Harper et al, Clin Infect Dis 2009;48:1003. Belongia et al, Lancet ID 2016, 16:942. 8
10/15/2018 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 9
10/15/2018 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% GGO predominant Consolidations + GGO Centrilobular nodules + GGO 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 10
10/15/2018 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. 11
10/15/2018 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. U SE OF P ROCALCITONIN IN V IRAL VS B ACTERIAL CAP PCT algorithm in patients with LRTI: ~2.5 day reduction in Abx Abx side effects mortality (8.6 vs 10.0%) Discrimination between viral vs. bacterial infection/coinfection (cut ‐ off 0.25): Sensitivity 70 ‐ 90%, NPV 80 ‐ 90% Bottom line: low PCT is a useful adjunct in immunocompetent floor patients 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. 12
10/15/2018 I NFLUENZA VS B ACTERIAL PNA: S UMMARY The problem: Severe influenza PNA and secondary bacterial PNA look the same clinically How to approach giving antibacterials? If severely ill empiric ABx while cultures pending If mild ‐ moderate illness use clinical judgment (PCT can be adjunct) When to stop empiric antibiotics? Respiratory cultures negative (before ABx) Low suspicion for bacterial infection (negative or minimal changes on CXR, low PCT) C ASE #1 C ONTINUED She was treated with oseltamivir and 2 days of Abx Tenuous clinically but recovered fully, still doing well as an outpatient. 13
10/15/2018 I NFLUENZA AND M YOCARDIAL I NFARCTION Increased risk (6x) of MI in the week following influenza True to a lesser extent for other respiratory viruses Other studies have shown similar results Mechanism: ?acute inflammation, increased demand Kwong et al, NEJM 2018. I NFLUENZA AND P AROTITIS 256 cases of influenza ‐ associated parotitis (“flumps”), almost all due to influenza A(H3N2) 27% adults, 69% male, 50 cases interviewed: 78% had ILI symptoms for 4 days before onset of painful swelling Unilateral in 68% (usually mistaken for bacterial) Elbadawi, Clin Infect Dis 2018, 67:493. Rolfes et al, Clin Infect Dis 2018, 67:485. Pavia, Clin Infect Dis 2018, 67:502. 14
10/15/2018 Case #2 A 35 year old man is admitted in January with 3 days of fever, cough and progressive respiratory distress. Rapid influenza antigen test in the ED is negative. W HAT IS THE S ENSITIVITY OF THE R APID A NTIGEN T ESTS ? 1. <25% 2. 30 ‐ 50% 3. 50 ‐ 70% 4. >90% 15
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