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

2. Upper Respiratory Infections (URIs)
Colds
Flu
Sinusitis
Pharyngitis

3. 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

4. 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

5. 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

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

8. 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

9. New York City Department of Health and Mental Hygiene

10. Influenza

11. Influenza Virus

12. 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 …

13. 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 … 

14. Burden of Yearly Influenza Epidemics

15. 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

16. 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

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

18. 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)

19. 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)

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

21. Influenza Vaccine: Effectiveness
RR (95% CI) for outcome among elderly vaccinated persons:
ELDERLY
(> 60 – 65)
Influenza
ILI
Hospitalization
Mortality
Nursing
homes
1.04 ( )
0.77 ( )
0.55 ( )
0.40 ( )
Community
0.19 ( )
1.05 ( )
0.73 ( )
0.53 ( )
0.73 ( )
(match)
0.48 ( )
0.48 ( )
(mismatch)
0.64 ( )
0.63 ( )
Data from large pooled studies (1990s-2000s) Lancet 2005;636:1165
NEJM 2007;357:13
Lancet Inf Ds 2014;14:1228

22. 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
49%
52%
19%
48%
42%

23. 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

24. 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

25. 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 ( )
Medicare cohort
(n=2,545,275)
0.78 ( )
0.78 ( )
VA cohort
(n=165,225)
0.99 ( )
1.05 ( )
VA subgroup > 85 yo
(n=21,826)
0.52 ( )
NEJM 2014;371:17
Lancet Inf Ds 2015;15:293
Clin Inf Ds 2015;61:171

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

27. 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

28. 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

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

30. 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%

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

34. 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

35. Influenza Treatment

36. Sinusitis

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

38. 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

39. 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

40. 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

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

42. 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

43. 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

44. 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

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

46. Pharyngitis

47. 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)

48. 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

49. 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

50. 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

51. 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

52. 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

53. Symptomatic Treatments for URIs

54. 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 +