SINUS INFECTION AND “BLOCKBUSTER DRUGS”
Educational Objectives
| The goal of this program is to provide up-to-date methods for managing sinus disease and selecting effective
drug therapies. After hearing and assimilating this program, the clinician will be better able to:
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 | 1. Describe sinus anatomy and its role in sinus infection.
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| 2. Define terms used for sinusitis, eg, acute rhinosinusitis and chronic rhinosinusitis.
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| 3. Identify organisms involved in sinus infections and antibiotics indicated for their treatment.
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| 4. Recognize ineffective, widely advertised and prescribed “blockbuster” drugs.
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| 5. Avoid potential risks associated with blockbuster drugs.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the faculty and planning committee reported nothing to disclose.
Acknowledgements
Dr. Reh was recorded at the Third Annual Infectious Diseases Update for the Primary Care Practitioner, sponsored by
the Johns Hopkins University School of Medicine, September 17-18, 2007, in Baltimore, MD; Dr. Finucane at the
35th Annual Current Topics in Geriatrics, sponsored by the Johns Hopkins University School of Medicine, January
17-19, 2008, in Baltimore. The Audio-Digest Foundation thanks Drs. Reh and Finucane, and the Johns Hopkins University
School of Medicine for their cooperation in the production of this program.
| A RATIONAL APPROACH TO SINUS INFECTION —Douglas X. Reh, MD, Assistant Professor of Medicine,
Johns Hopkins University School of Medicine, Baltimore, MD
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| Scope of problem: 35 million Americans get sinusitis each year; ≈25 million office visits annually; sinusitis most
common self-reported health condition
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| Sinus anatomy: pain referred through nerves innervating individual sinuses; maxillary sinuses—under cheeks; pain
referred to cheek or maxillary teeth and gums; ethmoid sinuses—between eyes; pain referred to between eyes, temple,
and periorbital region; frontal sinuses—over forehead; pain referred to supraorbital area or forehead; sphenoid
sinuses—back of nasopharynx (under pituitary; above adenoid pad); pain referred to retro-orbital or vertex (middle
of head)
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| Drainage: maxillary and anterior ethmoid sinuses drain to lateral nasal wall through ostia (small openings); frontal
sinuses drain through recess (often narrowed; posteriorly by anterior ethmoid cells; anteriorly by nasal mound [agger
nasi cell]); sphenoid sinuses drain anteriorly through ostia into posterior ethmoid region
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| Osteomeatal complex: narrow recess bounded medially by orbit; also bounded by anterior ethmoid cells and uncinate
process; natural anatomic bottleneck to drainage of anterior maxillary sinuses; sinonasal inflammation (from
virus or allergy) can close off region, leading to blockage of maxillary and ethmoid sinuses and secondary infection)
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| Definitions: agreed to by task force of specialists from American Academy of Otolaryngology, Academy of Otolaryngologic
Allergy, and American Rhinologic Society; rhinosinusitis—more specific than sinusitis; any nasal or
paranasal inflammation; acute rhinosinusitis—any sinonasal inflammation lasting ≤4 wk (viral or bacterial); chronic
rhinosinusitis—sinonasal inflammation lasting ≥12 wk
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| Guidelines for acute bacterial sinusitis: based on 2 major criteria or 1 major and 2 minor criteria
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| Major criteria: facial pressure or pain; nasal obstruction or blockage; discolored nasal discharge; hyposmia/
anosmia; purulence in nasal cavity on examination; fever
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| Minor criteria: headache; halitosis; fatigue; dental pain; cough; ear pain or congestion
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| Hallmark symptoms: have largely replaced major and minor criteria; most sensitive and specific for diagnosing
acute bacterial rhinosinusitis; facial pressure and pain; nasal obstruction; discolored nasal discharge
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| Imitators of acute rhinosinusitis
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| Allergic rhinitis: nasal blockage; nasal discharge
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| Septal deviation or enlarged turbinates: nasal obstruction
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| Migraine and dental disease: facial pressure and pain
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| Viral upper respiratory infection (URI): can cause all of the above symptoms; most difficult to differentiate from
acute bacterial sinusitis
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| Differential diagnosis: most acute bacterial sinusitis arises from preceding viral URI; however, only ≈0.5% to 1.0% of
viral URIs cause bacterial sinusitis; studies—used antral puncture of maxillary sinus as gold standard for diagnosing
bacterial sinusitis; no difference in signs or symptoms (eg, color of discharge) between viral URI and bacterial
sinusitis in first 3 to 4 days; suggestive of secondary bacterial infection—initial symptom improvement followed by
worsening at 5 to 7 days; after 10 days >70% of patients have bacterial sinusitis (diagnosis is time issue)
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| Clinical diagnosis: computed tomography (CT) of viral URI and bacterial sinusitis look same; nasal or nasopharyngeal
cultures also not helpful (do not correlate well with bacteria in sinuses)
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| Sinus headache and migraine: symptoms often overlap
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| International Headache Society (IHS) criteria for headache attributable to sinusitis: 1) frontal headache accompanied
by facial pressure or pain in cheeks, dental area, or ears; 2) clinical evidence of sinonasal inflammation on
endoscopy or CT; 3) headache and facial symptoms developed acutely, along with other symptoms suggestive of
rhinosinusitis; 4) headache or facial pressure resolves with adequate treatment of sinusitis
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| Differential diagnosis: consider sinusitis—patient presents with acute rhinogenic complaints, eg, nasal mucopurulence
and severe inflammation of mucosa, along with facial pressure, pain, and headache; consider migraine—patient with
long-standing stable pattern of daily headaches, without secondary or intermittent rhinogenic symptoms; recurrent
self-limited headaches, even with rhinogenic symptoms
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| Treatment: trial of antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs) appropriate; if symptoms persist,
consider CT; if CT normal, refer to neurologist for migraine work-up
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| Complications of sinusitis: based on location of sinuses
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| Orbital complications: from ethmoid or frontal sinuses
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| Preseptal cellulitis (group 1): inflammation or edema anterior to orbital septum; upper and lower eyelid edema;
generally not tender; gaze intact
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| Orbital cellulitis (group 2): inflammation extends back into orbit; presents with proptosis, gaze restriction, and
much pain; visual loss in severe cases
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| Subperiosteal abscess (group 3): in ethmoid sinusitis, abscess in potential space between periosteum and lamina
papyracea
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| Orbital abscess (group 4): in soft tissues of orbit
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| Differentiation between groups 2, 3, and 4: requires CT
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| Cavernous sinus thrombosis (group 5): same symptoms as groups 2, 3, and 4, but bilateral; bilateral involvement
pathognomonic for cavernous sinus thrombosis
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| Potts puffy tumor: expanding through anterior frontal sinuses into soft tissues of forehead; presents as large mass
on forehead (subcutaneous abscess connected to frontal sinus)
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| Organisms: 3 main organisms in uncomplicated acute bacterial sinusitis; drug resistance in each varies by area;
Streptococcus pneumoniae (penicillin-resistance ≈25%); nontypeable Haemophilus influenzae (30%-40% β-lactamase-positive);
Moraxella (90% β-lactamase-positive); β-lactamase-positive strains susceptible to amoxicillin
with clavulanic acid (Augmentin)
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| Speaker’s treatment recommendations: start with high-dose Augmentin; if patient recently treated with Augmentin
or allergic to penicillin, use levofloxacin (eg, Levaquin) or moxifloxacin (eg, Avelox)
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| First-line: sinonasal irrigation—(NielMed bottle filled with salt and baking soda solution); irrigation does not enter
sinuses, but forcefully removes secretions that block ostia, allowing sinuses to drain; nasal steroid—decongests
nose and helps open small ostia, allowing sinuses to drain
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| Second-line: topical decongestants; nasal spray (oxymetazoline [eg, Afrin])—for patients with moderate-to-high fever
and severe headache; use every 6 to 8 hr for ≤3 days; after 72 hr, rebound sinusitis develops; oral steroids—
reserved for patients who fail initial course of antibiotics; decongest nose
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| When to refer to otolaryngologist: after treatment failure; complicated sinusitis suspected; chronic sinusitis not
improving with antibiotics; nasal polyps present; therapeutic strategies—endoscopic culture; antral lavages; endoscopic
sinus surgery
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| Chronic sinusitis: inflammatory disease; swelling of lining of nose leads to nasal polyps; by—genetic causes (eg,
ciliary dysfunction); cystic fibrosis; aspirin triad disease (asthma; nasal polyps; asthma worsened by aspirin or
NSAIDs; dysregulation of prostaglandin pathway); poorly controlled allergies
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| Fungus controversy: Mayo Clinic identified fungus as major cause and patented fungal irrigations; no benefit
shown in prospective randomized placebo-controlled trials
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| Referral: all patients with chronic sinusitis should be referred to otolaryngologist
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| Medical management: culture-directed antibiotics during secondary acute infections; low-dose steroids; other anti-
inflammatory drugs; allergy evaluation and immunotherapy; antileukotrienes, eg, montelukast (Singulair); low-
dose macrolide antibiotic for anti-inflammatory effects; sinus surgery—patients eventually require ≥1 procedure
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| Questions and answers: nasal steroids for viral URIs—not recommended; advise patient that URI will clear in 5 to
7 days; sinus irrigations helpful; recurrent acute sinusitis—over time, bony remodeling develops; prevent by removing
nasal polyps; length of therapy—10 to 14 days of oral antibiotic required because bacterial sinusitis involves pus
trapped under pressure; if therapy limited to 5 days, add sinonasal irrigation and consider nasal steroid; therapeutic
strategy for rhinitis medicamentosa—oxymetazoline dependence; oxymetazoline nasal spray constricts nasal blood
vessels; blocks nutrients to nose; long-term use causes chronic edema and rebound inflammation, leading patient to
use more spray; weaning strategy (dilute oxymetazoline 25%-30% with nasal saline; use for 1 wk; then dilute remainder
50% and use for 1 wk; repeat until patient completely weaned); lining of nose returns to normal in 5 to 10 yr
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| BLOCKBUSTER DRUGS THAT DON’T DO MUCH —Thomas E. Finucane, MD, Professor of Medicine, Johns
Hopkins University School of Medicine, Baltimore
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| Definition: blockbuster drugs—any drugs selling >$1 billion annually to American public, often with very limited or
no evidence of efficacy and some signal of harm
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| Objectives: to recognize ineffectiveness of drugs; to identify manufacturers (corporations have legal duty to make
profits for investors; their goals very different from those of physicians); counsel patients about this; be wary of
“cheerleaders” (ie, drug representatives) and “chihuahuas” (susceptibility to advertising)
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| Proton pump inhibitors (PPIs): gastroesophageal reflux disease (GERD) poorly defined; could be abdominal
discomfort with heartburn after eating; sometimes requires endoscopic findings; abdominal discomfort (“bellyaching”)
common; misconception about adenocarcinoma—no evidence PPIs prevent (after widespread use, incidence of
adenocarcinoma of distal esophagus sextupled); evolutionary view—acid bath in distal foregut likely serves as primary
host defense mechanism; potential problems—chance of pneumonia doubles; risk for Clostridium difficile diarrhea
triples; risk for hip fracture almost tripled (poor calcium absorption)
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| Cholinesterase inhibitors: large randomized trial looked at use in clinically diagnosed Alzheimer’s disease (AD);
findings—no significant benefits with low- or high-dose donepezil, compared to placebo; no difference in institutionalization
or progression of disease; no significant benefit in behavioral or psychologic symptoms, caregiver
psychopathology, costs, time, adverse events, or death; only effect <1-point improvement on Mini-Mental State
Examination after 2 yr, and ≈1 point higher on 18-point activities of daily living scale (no meaning to patient or
caregiver)
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| Catastrophic deterioration if drug stopped: not found during washout periods in large trials
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| Donepezil as standard of care: idea based on American Academy of Neurology practice parameter on treatment of
dementia; statement actually says “cholinesterase inhibitors should be considered in patients with mild to moderate
AD (standard), although studies suggest a small average degree of benefit”
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| Overall trial results: recommendations do not seem to be evidence-based; benefits on rating scales minimal; methodologic
quality of trials poor
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| Atypical antipsychotics: mistakenly believed to have fewer extrapyramidal side effects; include risperidone
(Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel); no less risk for parkinsonism than haloperidol
(Haldol) at higher doses, eg, risperidone 2 mg, olanzapine 10 mg
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| Black box warning: required by Food and Drug Administration (FDA) on atypical antipsychotics, due to ≈60% increase
in mortality within first 10 wk of treatment in elderly patients with dementia; retrospective review indicates
same risk with conventional antipsychotics
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| Study: involved patients with AD and agitation, aggression, or psychotic features; compared 3 atypical antipsychotics
with placebo; drug withdrawn when toxicity outweighed benefit; results—each medication same as placebo in
time to discontinuation; minimal improvement; secondary analysis found slightly more efficacy with drug than
with placebo, with corresponding increase in toxicity
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| Cholinesterase inhibitors for agitation: 12-wk trial found donepezil no better than placebo in patients with AD
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| Sleeping pills: sleeping pills produce electroencephalography (EEG) different from that of normal sleep and do not
make sleep more restful; sleep study findings—patients who complain of insomnia greatly overestimate wakefulness;
patient claiming to be awake from 3:00 AM to 6:00 AM actually awake ≈15 to 20 min; primary insomnia
different from depression requiring treatment
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| Goals of sleeping pill: improve sleep quality; improve alertness, problem solving, and performance next day; trial
findings—5-fold increase in adverse cognitive effects, compared to placebo; increased adverse psychomotor effects
and daytime fatigue; benefits of sleeping pill never found in trial with objective measures of wakefulness or cognitive
performance; when objectively compared to placebo, sleeping pill improves sleep by <1 awakening per night,
with 0.5 hr longer total sleep time; however, sleep not normal, and performance next day worse
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| Recommendation: if compelled to prescribe medication, select short course of short-acting benzodiazepine (eg, oxazepam
[Serax], lorazepam [Ativan]); new sleeping pills starting with “z” (eg, zaleplon, zolpidem) ≈10 times
more costly and not more effective
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| Glitazones: while they lower hemoglobin A1c and fasting glucose level, no evidence of benefit; no trials in which
patients randomized to glitazones did better than patients with conventional control in producing outcomes
meaningful to patients, ie, amputation, stroke, myocardial infarction (MI), blindness, renal failure, or death
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| Black box warning: company influence stalled its inclusion for 8 yr; warns of risk for heart failure with pioglitazone
and rosiglitazone, and risk for ischemic disease for rosiglitazone
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| Erythropoietin stimulating agents (ESAs): heavily advertised and wildly overused
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| Black box warning: indicated for patients with cancer, only if anemia due to chemotherapy; may shorten survival
and speed tumor growth; should not be used to treat symptoms in any patient with cancer and anemia; use to limit
need for blood transfusion; stop after chemotherapy discontinued
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| Use in chronic kidney failure: pushing hematocrit higher than 36% leads to risk for MI, stroke, deep venous thrombosis
(DVT), heart failure, and death; if no benefit from ESA therapy, discontinue and reconsider problem
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| Web site addresses: www.fda.gov/medwatch; medicalletter.org; nofreelunch.org; citizen.org/hrg; www.nice.org.UK
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Suggested Reading
Benninger M: Guidelines on the treatment of ABRS in adults. In J Clin Pract 61:873, 2007; Benninger MS: Therapeutic
choices in the treatment of acute community-acquired bacterial rhinosinusitis. Am J Rhinol 20:662, 2006;
Clayman GL et al: Intracranial complications of paranasal sinusitis: a combined institutional review. Laryngoscope
101:234, 1991; Courtney C et al: Long-term donepezil treatment in 565 patients with Alzheimer's disease
(AD2000): randomised double-blind trial. Lancet 363:2105, 2004; Hadley JA et al: Oral beta-lactams in the treatment
of acute bacterial rhinosinusitis. Diagn Microbiol Infect Dis 57:47S, 2007; Laheij RJ et al: Risk of community-
acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 292:1955, 2004; Marple BF et al: Acute bacterial
rhinosinusitis: a review of U.S. treatment guidelines. Otolaryngol Head Neck Surg 135:341, 2006; Wang PS et
al: Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 353:2335,
2005.
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