1. Upper Respiratory Infections
Muhanad Taha

2. Objectives Upper Respiratory Infections Influenza Pharyngitis
Sinusitis
Bronchitis

3. A 26-year-old woman comes to clinic complaining of a "bad cold
A 26-year-old woman comes to clinic complaining of a "bad cold." She woke up three days ago with sore throat and rhinorrhea.  She complains of fatigue, and her nose is sore from frequent blowing. She has a headache. The most likely cause of her infection is:
a) Influenza
b) Rhinovirus
c) Adenovirus
d) Respiratory syncytial virus

4. Upper Respiratory Infections
Average is 2 to 4 URTIs.
Incidence peaks during the fall and winter
URTIs are nearly always caused by viral infection. Rhinovirus infection, the main cause of URTI #
# Next is coronavirus ,

5. The most effective means for prevention of future colds in this individual is: 
a) Smoking cessation
b) Regular exercise
c) Frequent hand washing
d) Vitamin C daily

6. Risk Factors
psychological stress is the most risk for development of URTI.
fomites are a major source for transmission so Poor hand hygiene is also a risk factor and prevention is best achieved through frequent hand washing
Smoking, a risk for lower respiratory infections not upper.  However, smoking does increaseduration and severity of URTI.8 
Asthma and emphysema also do not appear to increase the risk, but URTI can lead to exacerbations of both of these conditions.9,10
The majority of transmission of rhinoviruses occurs via fomites and is transferred from fomites via the hands to the nose, eyes, or mouth, from where the viruses then migrate to the nasopharynx.  Experimental infection has demonstrated that 75% of individuals who are infected develop symptoms, some as early as 10 hours after exposure.  Shedding of viral particles peaks 2 days after infection, but may continue at low levels for 1 to 3 weeks.3

7. A 56-year-old woman is diagnosed with an upper respiratory tract infection. She sees you today because her phlegm, previously clear, is now yellow/tan. Which of the following statements is true for this patient?
a) An antibiotic covering pneumococcus, Hemophilus, and Moraxella is indicated.
b) Antibiotic prophylaxis to prevent pneumonia is indicated if she has a fever.
c) Bacterial infection complicates 1/3 of all upper respiratory tract infections.
d) Reassurance is the most appropriate management.

8. Symptoms
Sore throat, sneezing , cough, nasal congestion, headache, sinus pressure
Symptoms are generalized, localizing symptom is present in (e.g., pharyngitis, sinusitis, or bronchitis)
purulent sputum and phlegm are not associated with bacterial infection or risk for bacterial infection. Cough may persist for several weeks after resolution of other symptoms.  When this occurs it is usually referred to as bronchitis or a 'chest cold.' 
rhinorrhea can becomes more purulent ,appearing thick and yellow to green. This change in nasal discharge results from recruitment of leukocytes, and is a natural part of the progression of a viral URTI.

9. Complication
The most common complication of URTI is exacerbation of underlying asthma or COPD.
Very rarely (i.e., <2% of cases) do URTIs progress to bacterial infection in adults, usually bacterial sinusitis or otitis media.
The most significant potential adverse outcome of having a URTI is inappropriately receiving antibiotics.  There is no evidence to support use of antibiotics for URTI to reduce duration, severity, or risk of complications.  
antibiotic prescribing does have 2 direct negative effects on patients: adverse drug effects and increasing the risk of a future infection with antibiotic resistant bacteria.
Most patient characteristics leading to prescribing antibiotics: current tobacco use, green or yellow nasal discharge or phlegm, and tonsillar exudates

10. Management Nasal congestion
# Oral decongestants such as phenylephrine and pseudoephedrine 
# topical nasal decongestants such as ipratropium (Atrovent) and Oxymetazoline (Afrin) “(rhinitis medicamentosa)
# First-generation antihistamines (e.g., diphenhydramine) are more effective than second-generation antihistamines (e.g., loratadine)
# No evidence for saline spray,lavage or steroids
cough
# avoid smoking and other irritations, oral fluids
# cough syrups containing dextromethorphan
# Oral decongestants such as phenylephrine and pseudoephedrine
Pharyngitis
# Oral analgesics
# Demulcent help decrease irritaion and inflamation
# No evidence of benefit for Zinc,vit C, gargle with salt water ,pepper.
Rhinitis Medicantosa: Rebound nasal congestion after stopping the topical nasal congestion. Usually when used >5days and more frequent than recommended.

11. Influenza
Regarding influenza virus, which one of the following statements about antigenic drift and antigenic shift is true?
a) Antigenic drift causes more severe outbreaks in a population than does antigenic shift.
b) Antigenic drift results from mutations in the HA and NA glycoprotein genes.
c) Antigenic drift can happen with influenza A, but is not described with influenza B.
d) Antigenic shift can happen with influenza B, but is not described with influenza A.

12. Microbiology influenza is an RNA virus 3 types: influenza A, B, and C.
hemagglutinin (H) and neuraminidase (N) are surface envelope glycoproteins in type A and B. These proteins change frequently.
Minor changes (antigenic drift) due to small and persistent mutations, are partly responsible for seasonal outbreaks or epidemics that occur almost yearly.
Major changes (antigenic shift) are alterations in the virus caused by reassortment of genes between human and animal influenza A strains. (only Influenza A infect animal) responsible for global influenza epidemics and pandemics, including the 2009 influenza A H1N1 swine-origin influenza pandemic
10 to 20% of the population infected each season in the United States.

13. 2009 Pandemic influenza
The highly pathogenic H5N1 avian influenza virus predominantly affects children and young adults recently exposed to infected birds and poultry in Europe and Asia. Person-to-person human transmission appears to be limited. The novel H7N9 influenza virus in China is also believed to result from exposure to infected poultry or contaminated environments. To date, no evidence of sustained person-to-person spread has been found.

14. Symptoms
Symptoms : Fever and Myalgia with other respiratory symptoms (sore throat,cough,nasal congestion)
Duration is 3-4 days, very rarely >7days in immunocompetent.
incubation period is 1-4 days
Risk of contagion is believed to be minimal 7 days after symptom onset#
influenza B is mild or asymptomatic,
Influenza infection occurs via respiratory secretions of infected persons. via large particle droplets
# in otherwise healthy patients. Viral carriage and shedding may be much longer in individuals with compromised immunity.27

15. Diagnosis
Consider the time of year as well as local influenza activity
 Influenza season occurs from October to April , Influenza is extremely rare in summer months
peak of activity in any area generally lasts less than 6 weeks. During this peak of activity, over 30% of patients with fever and cough have influenza. 

16. RT-PCR 
Molecular assay (influenza viral RNA or nucleic acid detection)
NP swab
1-8 hrs (rapid molecular assay <20mins)
High sensitivity and very high specificity; highly recommended; can differentiate between influenza types (A or B) and subtypes
Immunofluorescence
1-4 hrs
Moderately high sensitivity and high specificity; recommended
Detects and distinguishes between influenza A and B and between A/B and other respiratory viruses
Rapid Antigen detection (EIA)
<15 minutes
Low to moderate sensitivity and high specificity;
Detects but does not distinguish between influenza A and B

17. Differential Diagnosis
URI
Influenza
HIV
EBV
Headache, pharyngitis, nasal congestion , cough +
Fever
Absent or low grade
Maylgias/ Arthralgias NO
Rash -
5-10%
Common
70%
10%, only if antibiotics have been administered
Lymphdenopathy
Adenopathy is typically absent or minimal
Cervical 10-15%
70-75%
90-95%
Splenomegaly
10-15%
50%
Jaundice

18. A 43-year-old woman with diabetes presents for follow up
A 43-year-old woman with diabetes presents for follow up. She was diagnosed with influenza three weeks ago, and was treated with supportive care. She improved, but three days ago, productive cough and dyspnea worsened, along with new fevers. You obtained a chest x-ray today, which shows a left lower lobe infiltrate. Of the causes listed, which is the most likely etiology of her pneumonia?
a) Influenza A virus
b) Influenza B virus
c) Staphylococcus aureus
d) Pseudomonas aeruginosa

19. Complication
Complications include secondary bacterial pneumonia and cardiovascular compromise in patients with preexisting congestive heart failure or coronary artery disease.
Secondary bacterial pneumonia is the most common complication of influenza. The organisms involved are typically Streptococcus pneumonia, Haemophilus influenza, and Staphylococcus aureus;
 Saphylococcus aureus, particularly community acquired MRSA, is the most important pathogen to consider because it can cause a rapidly progressive necrotizing pneumonia and requires selection of antibiotics not usually used for community-acquired pneumonia.
Empiric antibiotic management for post-influenza pneumonia should follow general pneumonia treatment guidelines.  Adding vancomycin is appropriate for a patient with radiographic findings consistent with MRSA (necrotizing pneumonia), S. aureus on sputum gram stain, or if admitted to an intensive care unit for pneumonia management. 
Most influenza related mortality occurs indirectly as a result of complications of influenza rather than the influenza virus itself.

20. Which is the most appropriate approach for prevention of influenza?
 a) Live attenuated influenza vaccine
 b) Amantadine daily
 c) Oseltamavir daily
 d) Zanamivir daily
PREVENTION: Most effective intervention for preventing is Annual influenza vaccination, recommended for all >6months

21. You are treating a 26 y.o patient whom you suspect has influenza, presenting with 2-3 days of symptoms. There has not been an outbreak described in your community". Which statement is correct? a) Amantadine is effective treatment for both influenza A and influenza B infection. b) Resistance to oseltamivir is widespread; its use is no longer recommended. c) Zanamivir is ideal for treatment of influenza in asthma, since it is delivered via inhalation. d) Antiviral treatment is not indicated in this individual.

22. Management
Adults with mild illness without high-risk conditions who are younger than 65 years of age
# Is hospitalized
# Has severe, complicated or progressive illness
# Is at high risk for influenza complications (aged <2 years or >65 years, chronic pulmonary, cardiac, renal, hepatic, hematologic, or metabolic disease, immunosuppression including HIV, women who are pregnant, BMI>40, or resident in a nursing home)
If presented >48 hrs: No test or treatment needed (unless outbreak in community)
If present within48 hours of illness, antiviral treatment can be considered (grade 2C) in order to reduce the duration of illness
ACIP's guidelines and CDC guidline
The earlier antiviral given the more effective.
#Antiviral treatment should be initiated as soon as possible.
# Treatment should not be delayed while awaiting the results of diagnostic testing, # Don’t withheld in patients with indications for therapy who present >48 hours after the onset of symptoms, particularly among patients requiring hospitalization.

23. Management
Choice of antiviral therapy When treatment is required, the neuraminidase inhibitors oseltamivir and zanamivir are active against influenza A and B.  Peramivir, an intravenous neuraminidase inhibitor, was approved for use in adults in IV dose used in severe ill who can not tolerate oral or resistant to others
Treatment duration is generally 5 days but may be longer in immunocompromised or severely ill patients. Dosing of oseltamivir and peramivir must be modified in the setting of renal insufficiency.
Because of the high rates of influenza isolates resistant to adamantanes in the United States and in many other countries, amantadine and rimantadine are not recommended for the treatment of influenza.  However, season variation must be considered.  For example, during the influenza season, nearly 100% of seasonal H1N1 influenza was resistant to oseltamivir31. Fortunately, in the recent influenza seasons oseltamivir resistance has subsided to <5%. Thus oseltamivir is currently the agent of choice for the treatment of influenza. Zanamivir, peramivir, and the amantadine should only be used in special situations.

24. A 76-year-old with moderate to severe COPD has a history of a severe allergic reaction to an influenza vaccination 5 years ago.  He resides in a nursing home where 5 residents have recently been diagnosed with influenza.  Which is the most appropriate approach for prevention of influenza? 
a) Live attenuated influenza vaccine
b) Amantadine daily
c) Oseltamavir daily
d) Zanamivir daily

25. Prophylaxis
We recommend influenza prophylaxis for all residents during outbreaks in long-term care facilities regardless of prior influenza vaccination  (to control outbreak)
In unvaccinated individuals at high risk for influenza complications who have been exposed to an individual with influenza within the previous 48 hours, we recommend influenza prophylaxis (table 1) (Grade 1A). Such individuals should also be vaccinated against influenza and prophylaxis should be continued during the two weeks following influenza vaccination.

26. Pharyngitis Which of the following is correct regarding pharyngitis?
 a) The presence of a hoarse voice or laryngitis would make the diagnosis of bacterial pharyngitis more likely.
b) Extreme throat pain suggests bacterial causes of pharyngitis.
c) Among adults, throat culture should be obtained when the diagnosis of group A streptococcal pharyngitis is a possibility.
d) Fever is a warning sign that he has developed an invasive bacterial infection or peritonsillar abscess
e) The symptom complex of fever, tonsillopharyngeal exudates, cervical lymphadenopathy, and lack of cough suggests group A streptococcal pharyngitis.

27. Viral pharyngitis 90% of pharyngitis is viral in etiology
rhinoviruses, coronaviruses and adenoviruses.
Clinical features suggestive of viral pharyngitis include cough, hoarseness, rhinorrhea, conjunctivitis, rash, diarrhea, and the presence of stomatitis or ulcerative lesions in the oropharynx.

28. Bacterial pharyngitis
Group A beta-hemolytic Streptococcus (GABHS) (a.k.a. Streptococcus pyogenes) is the most common
Classic physical findings include fever, tonsillopharyngeal erythema (usually with exudates), and tender, enlarged anterior cervical lymph nodes
antibiotics are prescribed for 50 to 90% of cases seen in primary care visits due to concern for acute rheumatic fever 
Fortunately, acute rheumatic fever has become very rare in the United States among all age groups. This is believed to be a consequence of a shift in the antigenic structure of the predominant GABHS strain.

29. Complication
suppurative : peritonsillar abscess, cervical lymphadenitis, mastoiditis, sinusitis, and otitis media. There is insufficient data to conclude that antibiotic treatment for pharyngitis reduces the risk of these complications.
nonsuppurative complications:
Acute rheumatoid arthritis (GABHS)
Poststreptococcal reactive arthritis (PSRA)
Scarlet fever
Streptococcal toxic shock syndrome
Acute glomerulonephritis

30. Identifying and treating suspected cases of streptococcal pharyngitis is important.
Therapy for streptococcal pharyngitis can be delayed for up to 9 days and still prevent the onset of acute rheumatic fever.
role of antibiotics in preventing post-streptococcal glomerulonephritis from either pharyngitis or skin and soft tissue infections is unproven.

31. Lemierre’s syndrome : Jugular vein septic thrombophlebitis
Lemierre’s syndrome : Jugular vein septic thrombophlebitis. is a rare complication of either viral or bacterial pharyngitis
The causative organisms are usually members of the normal oropharyngeal flora mostly Fusobacterium necrophorum
Classic symptoms are high fevers and rigors occurring as early as two days after the onset of sore throat.44 On examination, tenderness is often detected over the sternocleidomastoid muscle. 
Septic jugular vein thrombosis can lead to septic emboli lodging in the lungs and the classic cannonball finding on computed tomography of the chest.
Treatment is with antibiotics with good anaerobic activity, such as ampicillin-sulbactam or clindamycin and consideration regarding surgical intervention and/or anticoagulation.
Classic example : Healthy patient presented initially with sore throat, fever, rapid strep test negative, diagnosed with viral pharyngtitis and sent home with symptoms control. Return back looks toxic, dehydrated,fever, worsening sore throat more lateral. Lateral tenderness over strenocleidomastoid. CXR showed ill-defined nodular opacities. CT neck w/ contrast showed occlusion of right jugular vein.

32. Lemierre’s syndrome

33. A 22-year-old woman presents with complaints of three days of sore throat and cough. On exam, she is febrile (T 38.3C), with tender anterior cervical adenopathy. Small white plaques are noted on her tonsils. Appropriate management at this point would be:
a) Empiric treatment with penicillin
b) Empiric treatment with amoxicillin
c) Rapid-strep antigen testing; antibiotics only if positive
d) Throat culture; penicillin now until resistance patterns known

34. Centor criteria

35. First-line antibiotic treatment for group-A beta-hemolytic streptococcal pharyngitis is:
Amoxicillin for 5 days
Penicillin for 10 days
Fluroquinolones for 5 days
Ceftriaxone for 10 days.

36. RSAT have high sensitivity and specificity (sensitivity 80-90%; specificity greater than 95%). The high accuracy of these tests eliminates the need for confirmatory bacterial culture among adults. Negative RSAT should not followed by culture
Antibiotics reduce the duration of streptococcal pharyngitis by 1 to 2 days, and reduce the risk of acute rheumatic fever even when initiated within 9 days of the onset of symptoms.
Penicillin is the recommended agent. Amoxicillin is endorsed as an alternative, offers no advantage.
Both antibiotics require a 10 day course to eradicate GABHS.
Macrolides (i.e., erythromycin, azithromycin) are an option for individuals with penicillin allergy,  

37. Sinusitis
Which ONE of the following statements is correct regarding sinusitits:
a) If maxillary sinus tenderness is noted on physical exam, bacterial sinusitis is likely.
b) Appropriate antibiotics is Ceftriaxone or Moxifloxacin.
c) Sinus CT should be obtained if bacterial sinusitis is diagnosed, to exclude osteitis or orbital cellulitis.
d) Factors that make acute bacterial sinusitis more likely include duration greater than seven days, unilateral facial pain, and worsening of symptoms after initial improvement.

38. Acute rhinosinusitis
inflammation of the paranasal sinuses and nasopharynx.
 Abnormalities in the maxillary sinus are observed among 87% of patients with URTI, regardless of whether symptoms localize to the sinuses
Mostly viral, bacterial is 10-20%

39. Symptoms
classic symptoms are nasal congestion, purulent nasal discharge, headache, maxillary tooth pain, facial pain that is worsened by bending forward.

40. Complication
complications are rare, estimated to occur in 1 per 10,000 cases of sinusitis. 
The main serious complications of bacterial sinusitis are local extension (e.g., osteitis, infection of the intracranial cavity, orbital cellulitis)
antibiotics do not play a role in preventing complications.

41. Antibiotics
antibiotics only in patients with :
- severe symptoms (fever, purulent drainage, and facial pain) for at least 3 days
- worsening of symptoms that were initially improving “doulble sickening”
- failure to improve with symptomatic treatment after 10 days.
The ACP recommends standard dose Amoxicillin/clavulanic acid (500/125) or doxycycline if allergic to penicillin as first line. 
Risk factors for resistence like recent antibiotics (within the past 6 weeks), comorbidities, immuncompromised, hospitalization past 5 days: High dose Amoxicillin/clavulanic acid (2000/125), doxycycline or moxifloxacin or levofloxacin
IF symptoms worsen after 3-5 days broad coverage or switch to another class.
Standard treatment duration for acute bacterial sinusitis is 10 to 14 days
Standard dose is 500/125
High dose 2000/125

42. 51-year-old presented with the chief complaint of cough
51-year-old presented with the chief complaint of cough. He states that symptoms began a week ago, when he had a cold. His cold symptoms resolved but cough remains. He notes production of green phlegm and some dyspnea as well as poor sleep due to frequent coughing. He has no emesis. On exam, he is afebrile. His pulse is 92, respirations are 18, and blood pressure is 112/68. On lung exam, wheezing is audible.
Which ONE of the following statements is correct?
 a) Treatment should be directed towards symptom management and does not include antibiotics.
 b) Purulent sputum suggests that antibiotics would help to clear the infection.
 c) Rhonchi indicate that his chest cold has now settled into the lungs, leading to pneumonia.
 d) Wheezing on exam suggests that he is having a COPD exacerbation rather than acute bronchitis.
 e) The symptoms are suggestive of infection with M. pneumoniae or C. pneumoniae. A course of macrolide antibiotics is indicated.

43. Bronchitis
Organisms that cause acute bronchitis ('chest cold') are often identical to those responsible for the common cold  rhinoviruses, coronaviruses, influenza, adenovirus, and respiratory syncytial virus.
Acute bronchitis usually begins as an upper respiratory tract infection or 'cold', followed by persistence of cough after resolution of other URTI symptoms, hence the term 'chest cold'.55 The cough usually tends to persist 1 to 2 weeks after the resolution of all other URTI symptoms, and may be either productive or non-productive.  Examination may be unremarkable, or rhonchi may be present. 

44. Differential diagnosis
Pneumonia is the most common serious condition to be excluded
other common causes of acute cough include pertussis, asthma, COPD exacerbation, and gastroesophageal reflux disease (GERD). 
5% have pneumonia, exclusion of pneumonia is important
If fevers or rigors and any of the following are present further evaluation for pneumonia with a chest x-ray is indicated: hemoptysis, pleuritic chest pain, tachypnea, tachypnea (RR>24 breaths/minute), hypoxia, examination findings of consolidation. 
Pertusis: Clinical suspicion of pertussis infection usually arises only when severe coughing persists after resolution of URTI symptoms. 
The appropriate diagnostic evaluation includes serology and PCR.
Macrolide antibiotics, such as erythromycin and azithromycin, are effective when started during the catarrhal phase, but have little role in later phases. Treatment of the paroxysmal and convalescent phases is supportive. 

45. It is not rare. Between % of patients with cough persisting greater than 1 week post-URTI have pertussis.
Clinical suspicion of pertussis infection usually arises only when severe coughing persists after resolution of URTI symptoms. 
The appropriate diagnostic evaluation includes serology and PCR.
Macrolide antibiotics, such as erythromycin and azithromycin, are effective when started during the catarrhal phase, but have little role in later phases. Treatment of the paroxysmal and convalescent phases is supportive. 
Pertussis may be prevented among adolescents and adults by administrating the acellular pertussis vaccine now combined with the tetanus booster vaccination, known as Tdap. 

46. Treatment
antibiotics are not indicated for acute bronchitis as mostly caused by virus.
Unfortunately, the rate of antibiotic prescription for bronchitis is approximately 70%
There is good evidence that beta-agonists, NSAIDs, and first generation antihistamines (e.g., diphenhydramine) all can reduce cough. Decongestants reduce mucus formation and cough
 Cough suppressants (dextromethorphan)have not proven to be beneficial in managing cough associated with acute bronchitis, although individual patients may experience symptomatic improvement.