It’s Getting to Be Flu Season: Effective Management of URIs Nicholas Fiebach, MD Department of Medicine Columbia University Medical Center

Upper Respiratory Infections (URIs) Colds Flu Sinusitis Pharyngitis

Upper Respiratory Infections (URIs) Colds Flu Sinusitis Pharyngitis Sinusitis (acute bacterial) 2% URIs 15% URI visits Strep pharyngitis (GABH) ~ 10% adult sore throat ~ 50% adults with URI complaints got antibiotics

Today’s Objectives Maximize flu vaccination Colds Distinguish specific syndromes which may benefit from antibiotics or antiviral rx Limit antibiotic rx Provide effective symptomatic treatments Colds Flu Sinusitis Pharyngitis

Microbial Etiologies of URIs VIRUSES rhinovirus coronavirus influenza parainfluenza respiratory syncytial virus (RSV) adenovirus enterovirus human metapneumovirus (HMPV) BACTERIA streptococcus (pneumonia, GABH, C and G) Haemophilus influenzae Moraxella catarrhalis

http://www1.nyc.gov/assets/doh/downloads/pdf/hcp/weekly-surveillance12302017.pdf

URIs: Clinical Epidemiology Incidence of respiratory infections Sep Dec Apr Adapted from Glezen Epidemiol Rev 1982;4:25

URIs: Clinical Epidemiology Incidence of respiratory infections influenza RSV parainfluenza rhinovirus mycoplasma enterovirus enterovirus Sep Dec Apr Adapted from Glezen Epidemiol Rev 1982;4:25

New York City Department of Health and Mental Hygiene http://www.nyc.gov/html/doh/flu/html/data/lab-surv.shtml

Influenza

Influenza Virus

INFLUENZA A SUBTYPES WHICH CAUSE WIDESPREAD DISEASE IN HUMANS HEMAGGLUTININ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 N E U R A M I …

INFLUENZA A STRAINS WHICH CAUSE WIDESPREAD OR SPORADIC DISEASE IN HUMANS HEMAGLUTININ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 N E U R A M I … 

Burden of Yearly Influenza Epidemics https://www.cdc.gov/flu/about/disease/burden.htm

Question #1 Which of the following persons should get influenza vaccine? 62 yo man with COPD 33 yo woman with asthma who is allergic to eggs 26 yo woman with acne 1 and 3 All of the above

Question #1 Which of the following persons should get influenza vaccine? 62 yo man with COPD 33 yo woman with asthma who is allergic to eggs 26 yo woman with acne 1 and 3 All of the above

Influenza Vaccine: Indications UPDATED INDICATIONS Age ≥ 50 yo √ Chronic illnesses Pregnant women Health care workers Caregivers < 6 months ≥ 65 yo

Influenza Vaccine: Indications UPDATED INDICATIONS Age ≥ 50 yo √ Chronic illnesses Pregnant women Health care workers Caregivers < 6 months ≥ 65 yo Chronic illnesses which increase risks for influenza illness, complications and mortality: Pulmonary Cardiovascular Renal Hepatic Neurologic, neuromuscular Hematologic Diabetes (and other metabolic ds) Immunosuppression Malignancy Morbid obesity (BMI > 40)

Influenza Vaccine: Indications UPDATED INDICATIONS Age ≥ 50 yo √ Chronic illnesses Pregnant women Health care workers Caregivers < 6 months ≥ 65 yo Age > 6 months (ie. almost everyone)

Influenza Vaccine: Effectiveness RR (95% CI) for outcome among healthy vaccinated persons: HEALTHY ADULTS Influenza ILI Hospitalization Mortality vaccine matched 0.38 (0.31-0.48) 0.84 (0.77-0.91) -- vaccine not matched 0.45 (0.34-0.59) 0.90 (0.69-1.18) Data from pooled studies in Cochrane Library 2014, Issue 3

Influenza Vaccine: Effectiveness RR (95% CI) for outcome among elderly vaccinated persons: ELDERLY (> 60 – 65) Influenza ILI Hospitalization Mortality Nursing homes 1.04 (0.43-2.51) 0.77 (0.64-0.96) 0.55 (0.36-0.84) 0.40 (0.21-0.77) Community 0.19 (0.02-2.01) 1.05 (0.58-1.89) 0.73 (0.67-0.79) 0.53 (0.46-0.61) 0.73 (0.68-0.77) (match) 0.48 (0.39-0.51) 0.48 (0.46-0.51) (mismatch) 0.64 (0.52-0.78) 0.63 (0.57-0.69) Data from large pooled studies (1990s-2000s) Lancet 2005;636:1165 NEJM 2007;357:13 Lancet Inf Ds 2014;14:1228

Influenza Vaccine: Effectiveness Year-to-year variation related to circulating strains and vaccine match: overall reduction across the US population in acute respiratory illness associated with influenza A and B virus infections among vaccinated persons 2012-13 49% 2013-14 52% 2014-15 19% 2015-16 48% 2016-17 42%

Influenza Vaccines 2017-18 Trivalent (1 A-H1N1, 1 A-H3N2 and 1 B) standard-dose trivalent shot  IIV3   standard-dose trivalent jet injector needle free high-dose trivalent shot hdIIV3 > 65 yo trivalent shot grown in cell culture ccIIV3 > 18 yo (but not egg-free) recombinant trivalent shot RIV3 egg-free ( > 18 yo) adjuvanted trivalent shot aIIV3 Quadrivalent (1 A-H1N1, 1 A-H3N2 and 2 B) standard dose quadrivalent shot IIV4  AIM this year intradermal quadrivalent shot smaller needle (< 65 yo) recombinant quadrivalent shot RIV4 quadrivalent nasal spray LAIV 18 – 49 yo not recommended

Influenza Vaccines 2017-18 Trivalent (1 A-H1N1, 1 A-H3N2 and 1 B) standard-dose trivalent shot  IIV3   standard-dose trivalent jet injector needle free high-dose trivalent shot hdIIV3 > 65 yo (AIM this year) trivalent shot grown in cell culture ccIIV3 > 18 yo (but not egg-free) recombinant trivalent shot RIV3 egg-free ( > 18 yo) adjuvanted trivalent shot aIIV3 > 65 yo Quadrivalent (1 A-H1N1, 1 A-H3N2 and 2 B) standard dose quadrivalent shot IIV4 intradermal quadrivalent shot smaller needle (< 65 yo) recombinant quadrivalent shot RIV4 quadrivalent nasal spray LAIV 18 – 49 yo not recommended

Influenza Vaccine Effectiveness: High Dose v. Standard Dose Risk (95% CI) of outcome among vaccinated persons >65 yo: Influenza ILI Hospitalization Mortality RCT (n=31,989) 0.76 (0.63-0.90) Medicare cohort (n=2,545,275) 0.78 (0.71-0.85) 0.78 (0.73-0.84) VA cohort (n=165,225) 0.99 (0.86-1.16) 1.05 (0.87-1.26) VA subgroup > 85 yo (n=21,826) 0.52 (0.29-0.92) NEJM 2014;371:17 Lancet Inf Ds 2015;15:293 Clin Inf Ds 2015;61:171

Influenza Vaccine: Timing As soon as available Ideally by October Through the end of influenza season (Feb-Mar) Immunity develops over 2 weeks

Influenza Vaccine: Adverse Effects Inactivated/parenteral sore arm (common) constitutional (10% - fever, headache, myalgias) anaphylaxis (very rare, if not egg allergic) Guillain-Barre (rare) Flu – NEVER

Influenza Vaccination: Patient Resistance Efficacy emphasize reduction in hospitalization and mortality Fear of side effects emphasize coincidence of URIs and flu vaccination seasons Never or not recently vaccinated improvement in available vaccines Make a strong recommendation

Influenza Clinical Diagnosis Best predictors: fever ( ~ 100o F or higher) cough acute onset 80-90% positive predictive value when influenza is circulating

Influenza Diagnostic Tests Method Types Detected Acceptable Specimens Test Time Sensitivity Specificity RT-PCR  A and B NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum Varied (1-6 hours) Very high Rapid Influenza Diagnostic Tests NP swab, (throat swab), nasal wash, nasal aspirate <30 min. 40 – 70% 90 – 95%

Influenza Clinical Diagnosis Interpreting clinical findings and making treatment decisions depends on knowing if influenza is circulating: CDC hotline, website (www.cdc.gov) State and local health departments (www.nyc.gov) Local surveillance networks Hospital labs Local wisdom and media

http://www1.nyc.gov/assets/doh/downloads/pdf/hcp/weekly-surveillance12302017.pdf

https://www.health.ny.gov/diseases/communicable/influenza/surveillance/2017-2018/flu_report_current_week.pdf

Influenza - Testing and Treating Influenza-like Illness (ILI): T > 100.4°F (38°C) and cough or sore throat Mild-moderate symptoms or signs Moderate - severe symptoms or signs No underlying conditions Underlying conditions Refer to ED or hospital for evaluation, testing, and treatment Do not test Home isolation ? Treat Do not test Home isolation Treat

Influenza Treatment

Sinusitis

Diagnosis of acute bacterial sinusitis From Williams JW Jr, Simel DL. JAMA 1993;270:1242-6

Question #2 A 50 yo man comes to the office for nasal congestion with yellow rhinorrhea and “sinus pain” for the past 3 days. He is afebrile with mild maxillary tenderness bilaterally. You should: Order a single Waters view sinus x-ray Rx azithromycin (Z-Pak) x 5 days Rx amoxicillin-clavulanate (Augmentin) x 10 days Rx a decongestant 2 and 4

Question #2 A 50 yo man comes to the office for nasal congestion with yellow rhinorrhea and “sinus pain” for the past 3 days. He is afebrile with mild maxillary tenderness bilaterally. You should: Order a single Waters view sinus x-ray Rx azithromycin (Z-Pak) x 5 days Rx amoxicillin-clavulanate (Augmentin) x 10 days Rx a decongestant 2 and 4

Diagnosis of acute bacterial sinusitis Previous history of sinus disease not necessarily informative Symptoms not sufficiently specific individually, but combinations are suggestive colored nasal discharge unilateral maxillary pain (facial, tooth) symptoms lasting longer than 7-10 days, or worsening after initial improvement Unreliable signs percussion transillumination

Imaging acute bacterial sinusitis Sensitivity Specificity Xrays good (90%) fair (80-85%) CT excellent (>90%) poor

Imaging acute bacterial sinusitis Bottom line: not recommended for most patients who present with acute symptoms suggesting sinusitis. helpful in the evaluation of patients with: unexplained headache poor response to therapy severe symptoms or who are toxic and require accurate diagnosis early recurrent episodes of suspected acute bacterial sinusitis

Empiric diagnosis of acute bacterial sinusitis Purulent nasal discharge reported or observed or Maxillary tooth or facial pain, tenderness on exam days Persistent > 10 Severe, with fever > 3 Worsening of nasal or sinus symptoms after initial improvement > 5

Antibiotics for sinusitis Recommended regimens allergic to penicillin amoxicillin 500 mg 3 times daily for 5-7 days doxycycline 100 mg twice daily for 5-7 days amoxicillin/clavulanate 500 mg/125 mg 3 times daily for 5-7 days levofloxacin 500 mg once daily for 5-7 days 875 mg/125 mg twice daily for 5 days* moxifloxacin 400 mg once daily for 5-7 days * my preference to maximize spectrum, potency and adherence

Treatment of sinusitis Antibiotics NOT recommended: Macrolides (azithromycin, clarithromycin) Trimethoprim/sulfamethoxazole Adjunctive treatment: Nasal steroid Saline irrigation Topical and systemic decongestants

Pharyngitis

Practical approach to pharyngitis in adults Exclude severe forms of bacterial pharyngitis Peritonsillar abscess Retropharyngeal abscess Epiglottitis F necrophorum/Lemierre’s syndrome Assess for Group A Beta-Hemolytic Strep (GABHS)

Clinical predictors of GABHS Centor criteria: Tonsillar exudate Tender anterior cervical lymph nodes History of fever or temp > 38 C (100.4 F) Absence of cough

Testing and Treating GABHS Pharyngitis Clinical predictors (Centor criteria): Tonsillar exudate Tender anterior cervical lymph nodes History of fever or temp > 38 C (100.4 F) Absence of cough # predictors PPV NPV Clinical Management 3 - 4 40-60% Test or treat empirically 0 - 2 Do not test or treat Rapid tests 65% 98% Treat if positive

Antibiotic Treatment for GABHS Pharyngitis Benzathine penicillin 1.2 x 106 u IM Penicillin VK 500 po bid x 10 days Penicllin allergic w/o anaphylaxis: Cephalexin Cefadroxil 1000 po qd x 10 days Penicillin allergic w/ anaphylaxis: Azithromycin* Clarithromycin* Clindamyin 500 po qd x 5 days 250 po bid x 10 days 300 po tid x 10 days * Not for empiric treatment when F necrophorum a possibility

Summary: specific treatment for URIs Acute cough and fever during flu season Neuraminidase inhibitor, especially if severe or high risk Prolonged or severe nasal and/or facial symptoms Antibiotic for bacterial sinusitis 3 or 4 Centor criteria for strep throat or positive rapid test Penicillin for GABHS

Summary: specific treatment for URIs Acute cough and fever during flu season Neuraminidase inhibitor, especially if severe or high risk Prolonged or severe nasal and/or facial symptoms Antibiotic for bacterial sinusitis 3 or 4 Centor criteria for strep throat or positive rapid test Penicillin for GABHS all other URIs

Symptomatic Treatments for URIs

Targeted Treatment of URI Symptoms THERAPY EVIDENCE Analgesics – oral ? Analgesics – topical Decongestants – oral ± Decongestants – topical Antihistamines Expectorants Vitamin C + (higher doses) Echinacea - Zinc lozenges Chicken soup +