Upper Respiratory Tract Infections Masoud Mardani. M. D. MPH, FIDSA

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2 Upper Respiratory Tract Infections Masoud Mardani. M. D. MPH, FIDSA Professor Of Infectious Diseases Shahid Beheshti Medical University

3 URTI s Sinusitis Acute Otitis Media Pharyngitis

4 Question One: What percent of adults with common colds progress to acute bacterial sinusitis? A) 5-10% B) 2-5% C) 0.5-2% D) %

5 Sinusitis Most often a secondary infection of the paranasal sinuses which occurs because the outflow from one of the sinuses is decreased Common cold is really a viral rhinosinusitis 87% of patients with common colds have CT evidence of sinus cavity disease 0.5-2% will progress to acute bacterial sinusitis Maxillary sinus is most often affected [J Gen Int Med 1992; 7:481] & [Clin Inf Dis 1996; 23:1209]

6 Impact of Sinusitis in the US The estimated number of cases of acute bacterial sinusitis is million per year Approximately 10% seek medical care leading to 2 million office visits per year Cost of medications is more than $3 billion dollars per year, not including antibiotics Bartlett, 2001

7 Sinusitis: Predisposing Factors Impaired mucociliary function: > viral URTI s > cold or dry air > chemicals & drugs > cystic fibrosis > ciliary dysmotility syndrome Obstruction of sinus ostia: > anatomic abnormalities > allergic rhinitis > rhinitis medicamentosa > viral URTI s Vortel & Chow, 1992

8 Sinusitis: Predisposing Factors Immune defects: > IgA deficiency > AIDS > IgG subclass deficiency > diabetes > Wegener s granulomatosis Increased risk of microbial invasion: > odontogenic infection > head trauma > nasotracheal intubation > cocaine use > swimming or diving Vortel & Chow, 1992

9 Causes of Acute Maxillary Sinusitis Bacterial agents Mean Range S. pneumoniae 31% 20-35% H. influenzae 21% 6-26% S. pneumoniae & H. influenzae 5% 1-9% M. catarrhalis 2% 2-10% Viral agents Rhinovirus 15% Influenza 5% Parainfluenza 3% Gwaltney, 1996

10 Antibiotic Resistance S. pneumoniae mechanism: altered penicillin binding proteins high-level and overall resistance is on the rise incidence varies widely with location H. influenzae about 30% of isolates produce beta-lactamase M. catarrhalis over 90% of isolates produce beta-lactamase Bartlett, 1997

11 Microbial Causes of Sinusitis More than half of the cases of acute sinusitis are caused by S. pneumoniae & H. influenzae Anaerobes and S. aureus are uncommon but may be associated with chronic sinusitis Fungi seen in hosts with impaired immunity Nosocomial sinusitis is most often due to Gram-negative rods or S. aureus Bartlett, 1999

12 Acute Sinusitis is Overdiagnosed 174 patients clinically diagnosed with sinusitis, only 89 (53%) confirmed by sinus puncture In contrast to clinical features, ESR and CRP helped predict which patients had culture proven sinusitis For patients with abnormal ESR and CRP, sensitivity was 82% and specificity was 57% Hansen et al, 1995

13 Question Two : A 52 year old woman presents with 3 days of headache, tooth pain, and purulent nasal discharge unresponsive to decongestants. Her exam is normal. What do you believe? A) I m sure this is the the common cold B) Likelihood this is sinusitis is < 40% C) Likelihood this is sinusitis is > 60% D) Can t tell to any degree of certainty

14 Question Two (part 2): Would you treat this patient with an antibiotic? A) Yes B) No

15 Features That Predict Sinusitis Clinical Feature Likelihood ratio Maxillary toothache 2.5 ( ) Purulent secretion by exam 2.1 ( ) Poor response to decongestant 2.1 ( ) Abnormal transillumination 1.6 ( ) Hx of colored nasal discharge 1.5 ( ) [JAMA 1993; 270:1242-6]

16 Probability of Sinusitis Number of Predictors Probability (%) Williams et al, 1992

17 Diagnosing Acute Sinusitis If less than two of the five clinical features described by Williams and co-workers [Ann Intern Med 1992; 117: 705] are present, sinusitis is effectively ruled out If four of the five clinical features are present, sinusitis is effectively ruled in If 2-3 features present, consider x-rays Canadian Sinusitis Symposium, 1997

18 Sinus Transillumination In a dark room, place light source on infraorbital rim and look at roof of the mouth Result # of Sinuses Positive Aspirates Normal 18 1 (6%) Dull 26 7 (27%) Opaque (100%) Gwaltney et al, 1981

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20 X-rays and Diagnosing Sinusitis A single Waters view is sufficient Williams et al, 1992 Good correlation seen in only 50% (major problem is many false positives with x-rays) Bartlett, 2001 Air-fluid level is most reliable: in 18 patients with this finding, 16 had positive aspirates Gwaltney et al, 1981

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22 CT Scans in Diagnosing Sinusitis CT is best imaging technique & limited scans are now costing less Bartlett, 2001 CT may be too sensitive: Of 666 patients who had CT scan for either head trauma or seizures, % 43 had abnormal sinuses, %24 involving the maxillary sinuses Havas et al, 1988

23 Indications for Sinus CT Imaging Patient is considered a candidate for surgery Acute sinusitis with suspected intracranial or intraorbital extension Patient with severe facial pain or headache when nasal endoscopy is not diagnostic Patient fails to respond to standard therapy, including antibiotic treatment Bartlett, 2001

24 Cultures for Diagnosing Sinusitis Cultures of purulent nasal discharge contaminated by organisms in the nose Endoscopic collection: 65% sensitive and 40% specific compared to sinus aspirate Aspirate of sinus is definitive: obtain Gram stain as well as aerobic & anaerobic cultures (fungal stain & culture if compromised) [Clin Inf Dis 1996; 123:1209] & [ICAAC 1995; Abs D42]

25 Indications for Sinus Aspiration Septic or immunocompromised patient Nosocomial infection Poor response to therapy Complications > meningitis > brain abscess (frontal) > periorbital cellulitis > osteomyelitis > cavernous sinus thrombosis Bartlett, 1997

26 Management of Sinusitis Rule out dental source and complications Surgical management to promote drainage, remove diseased tissue, or correct ostial and/or intranasal abnormalities Consider hospitalization if patient is acutely ill or immunocompromised, if complication occurs, or if the frontal sinus is involved Goodman & Slavin, 1994

27 Medical Management of Sinusitis - Steam can prevent nasal crusting & liquefy secretions Steam can prevent nasal crusting & liquefy secretions steam inhalation several times daily Saline can prevent nasal crusting & liquefy secretions saline nasal spray qid Decongestants help to increase ostial diameter topical oxymetazoline (0.05%) 2-3 sprays in each nostril bid x 3 days at start of therapy; watch for rebound effect pseudoephedrine mg qid Goodman & Slavin, 1994

28 Medical Management of Sinusitis - 2 Topical steroids reduce mucosal inflammation; limit use to chronic sinusitis due to allergies beclomethasone 2 sprays in each nostril bid many other agents now available Mucoevacuants thin mucous secretions guaifenesin mg bid Antibiotics eradicate bacterial infection shown to be of benefit in numerous clinical trials Wald et al (1986) showed placebo effect is > 40% Goodman & Slavin, 1994

29 Question Three: First line therapy for acute sinusitis is: A) Amoxicillin-clavulanate B) Cefprozil C) Levofloxacin D) Azithromycin E) Amoxicillin

30 What is the correct duration for treating acute bacterial sinusitis with antibiotics? A) Three days B) Ten days C) Fourteen days D) Twenty-one days

31 Which Antibiotic to Choose? Historically established amoxicillin, doxycycline, TMP-SFX FDA-approved for sinusitis amoxicillin/clavulanate, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil, ciprofloxacin, clarithromycin, gatifloxacin, loracarbef, levofloxacin, and moxifloxacin Bartlett, 2001

32 Antibiotics With Proven Efficacy* by Pre- and Posttreatment Aspiration Amoxicillin amoxicillin-clavulanate cefdinir cefuroxime axetil 500 mg po tid 875/125 mg po bid 300 mg po bid mg po bid cefpodoxime gatifloxacin loracarbef trimethoprim-sulfamethoxazole levofloxacin moxifloxacin mg po bid 400 mg po q day 400 mg po bid one DS po bid 500 mg po q day 400 mg po q day *pathogen eradication in > 90% Bartlett, 2001

33 Therapy for Acute Sinusitis Gold standard: Amoxicillin Bartlett, 2001 CDC Recommendation: Amoxicillin O Brien, 1998 Amoxicillin therapy should be the firstline treatment of acute bacterial sinusitis Canadian Sinusitis Symposium, 1997

34 How Good is Amoxicillin? Meta-analysis looking at effect of antibiotics versus lacebo (and amoxicillin or TMPSFX versus more expensive antimicrobials) 2717 patients with acute sinusitis from 27 trials Compared with placebo, antibiotics decreased the incidence of clinical failures by half (RR = 0.54 with 95% confidence interval ) amoxicillin and TMP-SFX equal to the rest [BMJ 1998; 317:632-7]

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36 Duration of Antibiotic Therapy Most clinical trials have used days 1997 Canadian Sinusit is Symposium has formally recommended a 10 day course Evidence that three days may be enough: > trial of amoxicillin/clavulanate vs. amoxicillin in children with sinusitis [Wald et al, 1986] clinical response after 3 days was equal to 10 days > 80 adults treated with TMP-SFX [Williams et al, 1995] no difference between 3 and 10 days of therapy all received 3 days of oxymetazoline

37 Question Four: A 2 year old girl presents with a 1 day history of irritability, fever, and ear pain. On exam you see a bulging & red tympanic membrane. Do you treat her with antibiotics? A) Yes B) No

38 Acute Otitis Media Definition: presence of fluid in the middle ear accompanied by signs of acute illness Most common pediatric problem by age 3, more than 75% have been affected major cause of meningitis, sepsis, and hearing loss Predisposing factors include: eustachian tube obstruction (URTI s & allergies) anatomy of child s middle ear Klein, 1994

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40 Causes of Acute Otitis Media S. pneumoniae 25-50% H. influenzae 15-30% M. catarrhalis 3-20% Respiratory viruses 20% S. pyogenes 2-3% S. aureus 2-3% [Clin Infect Dis 1994; 19:823-33]

41 Diagnosis of Acute Otitis Media Signs & symptoms: ear pain, ear drainage, hearing loss, lethargy, irritability, & fever Tympanic membrane is full & bulging, often red and immobile, occasionally perforated Middle ear effusion determined by exam, through pneumatic otoscopy, or impedance tympanometry Berman, 1995

42 A: Painful, retracted eardrum (due to negative pressure and not acute otitis media) B: Bulging eardrum with purulent fluid consistent with acute otitis media C: Red tympanic membrane without middle ear fluid is not otitis media

43 Indications for Tympanocentesis Neonates Immunocompromised patients septic patients Toxic patients despite > 2 days of therapy Recurrent disease Onset during antibiotic therapy Complications: meningitis or mastoiditis

44 Management of Acute Otitis Media Analgesics may help relieve symptoms Decongestants & antihistamines are unproven Role of antibiotics is becoming controversial concern with emergence of resistance (Berman, 1995) must treat 7 children to improve one (Rosenfeld, 1995) antibiotic use associated with decrease in incidence of mastoiditis & meningitis (Bluestone, 1995); but much of this decline is due to the Hib vaccine (CDC, 1996) Must follow-up patient to assess response

45 Therapy for Acute Otitis Media Amoxicillin is the drug currently preferred for initial empiric therapy of acute otitis media Bluestone, 1995 Amoxicillin remains the drug of choice for treatment of acute otitis media because of its 20-year record of clinical success, acceptability, limited side effects and relative low cost. Klein, 1994

46 1999 CDC Recommendations Amoxicillin is still first line, regardless of prevalence of penicillin resistance Increasing penicillin resistance seen with S. pneumoniae so use higher dose Dose is now mg/kg/day x 10 days Standard dose of mg/kg/day may be used if risk of resistance is low (e.g. age > 2, no day care, no antibiotics in past 3 months) [Pediatr Infect Dis J 1999; 18:1-9]

47 1999 CDC Recommendations Alternative agent should be considered after three days if amoxicillin fails Agent should cover H. influenzae, M. catarrhalis and penicillin resistant S. pneumoniae Cefuroxime 30 mg/kg divided bid, or Amoxicillin-clavulanate mg/kg/day (amoxicillin component mg/kg/day with clavulanate dosing remaining at approximately 10 mg/kg/day), or Ceftriaxone 50 mg/kg IM q day x three doses [Pediatr Infect Dis J 1999; 18:1-9]

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49 Persistent Middle Ear Effusion Seen in 70% at 2 weeks, 20% at 2 months Associated with hearing loss If middle ear effusion persists at 12 weeks: antibiotic as in acute otitis media, but for 14-21days plus prednisone 1 mg/kg/d divided bid for 1 week If middle ear effusion persists at 16 weeks: check audiometry; refer for tympanostomy tubes if bilateral hearing threshold > 20 db Berman, 1995

50 New Vaccine for S. pneumoniae Conjugate 7-valent vaccine targeted at S. pneumoniae was approved in 2000 Doses at 2, 4, 6 and months Vaccine efficacy: 97% reduction in bacteremia and meningitis 73% reduction in pneumonia 34% reduction in otitis media [Infectious Disease News, 1999] [MMWR 2000; 49(RR-9):1-35]

51 Question five: An 18 year old man presents with sudden onset of fever and sore throat on Friday. You see patchy exudates over the tonsils but the rapid strep screen is negative. Do you get a culture in case the rapid detection test is negative? A) Yes B) No

52 Causes of Pharyngitis Rhinovirus 20% Coronavirus > 5% Adenovirus 5% Herpes simplex virus 4% Group A Streptococcus 15-30% Group C Streptococcus 5-10% Unknown 30%

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54 Hints to Determine Cause of Pharyngitis Influenza: cough & constitutional symptoms Adenovirus: conjunctivitis EBV: splenomegaly & retrocervical nodes HIV: rash and diffuse lymphadenopathy HSV: stomatitis or vesicles Diphtheria: pseudomembrane Numerous viruses: hoarseness Bartlett, 1997

55 Streptococcal Pharyngitis Typical features include sudden onset of fever, chills, severe sore throat, dysphagia, malaise, and headache Examination typically shows pharyngeal erythema, exudative pharyngitis and anterior cervical lymphadenopathy None of these features are diagnostic Bartlett, 1997

56 Features Suggestive of S. pyogenes Scarlitiniform rash: tiny red papules initially involving the face; rash appears 1-2 days after sore throat and resolves in 7-10 days; desquamation of palms & soles may occur Age: S. pyogenes causes 50% of pharyngeal infections in school age children (6-17 years old), but less than 10% in adults over 30 Bartlett, 1997

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58 Diagnosis of Streptococcal Pharyngitis Gold standard is throat culture 100% specific & 90-95% sensitive Rapid antigen detection tests (strep screens) > 95% specific but only 80-90% sensitive If rapid antigen screen negative, get culture Bottom line: treat if any test is positive!! IDSA, 1997

59 Complications of Streptococcal Pharyngitis Acute rheumatic fever Poststreptococcal glomerulonephritis Scarlet fever Peritonsillar abscess Streptococcal toxic shock syndrome Epiglottitis

60 Management of Pharyngitis Treat if suspicion is high but confirm case Bisno et al, 1997 Treatment within 9 days from symptom onset will prevent acute rheumatic fever Catanzaro, 1954 Symptoms improve in 3 days, even when not treated, slightly less when treated (patients are non-infectious after 24 hrs) Bartlett, 1999

61 Therapy for Streptococcal Pharyngitis In children: penicillin 250 mg bid or tid x 10 days (amox ok) benzathine penicillin 0.6 million units IM once erythromycin mg/kg/d divided qid x 10 days in patients with penicillin allergy In adults: penicillin 250 mg tid (or 500 mg bid) x 10 days benzathine penicillin 1.2 million units IM once if allergic, erythromycin 250 mg qid x 10 days IDSA, 1997

62 Once Daily Therapy for Strep Throat 152 children with strep throat randomized to receive either amoxicillin 750 mg po once daily or penicillin 250 mg po tid x 10 days Adherence monitored by urine testing and throats were cultured 1-3 weeks after Rx No difference between bacteriologic failures in either arm [Pediatrics 1999; 103:47-51]

63 Follow-up of Streptococcal Pharyngitis Only work up contacts if they have history of rheumatic fever, or if they have persistent or recurrent pharyngitis Follow-up cultures only indicated if symptoms persist, patient has history of rheumatic fever, or outbreak is present IDSA, 1997

64 Recurrent Streptococcal Pharyngitis Probably due to beta-lactamases produced by other organisms in oropharynx If recurrence does occur: clindamycin children: mg/kg/d divided tid x 10 days adults: 150 mg qid x 10 days amoxicillin/clavulanate 40 mg/kg/d divided tid x 10 days IDSA, 1997

65 Conclusions Upper respiratory tract infections cause a significant amount of morbidity in the US S. pneumoniae, H. influenzae, and S. pyogenes are the major organisms involved Simple and inexpensive medications are still the agents of choice for these infections Judicious use of antibiotics will help control costs and minimize the spread of resistance

66 Thank You!!