Title: PharmaNote
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Permanent Link: http://ufdc.ufl.edu/UF00087345/00067
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Title: PharmaNote
Series Title: PharmaNote
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Creator: University of Florida College of Pharmacy
Publisher: College of Pharmacy, University of Florida
Publication Date: September 2008
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Joshua Bell, Pharm.D. candidate

Although sinusitis may be self-limiting, its
toll on healthcare is vast. Sinusitis affects 16% of
the U.S. adult population with an overall direct an-
nual health care cost of $5.8 billion.1 Sinusitis re-
sults in Americans spending $2 billion on over the
counter medications, filling 15 million antibiotic pre-
scriptions, and attending 17 million office visits an-
nually.2 One in five antibiotic prescriptions are for
patients with sinusitis symptoms.3 However, wide-
spread use of conjugate pneumococcal vaccine has
led to a modest decrease in the incidence of infec-
tious acute sinusitis.4
There are numerous potential implications
and collateral damage with over diagnosis of sinusi-
tis and subsequent unnecessary treatment with antibi-
otics. Approximately 38% of adults presenting with
symptoms of sinusitis actually have a bacterial infec-
tion.5 Antibiotics are frequently prescribed for acute
sinusitis, even though the causative agent may be
viral in origin. Viral sinusitis typically resolves
within three weeks without the need for antibiotics;
although, viral upper respiratory tract infections
(URTI) often precede acute sinusitis.1 Injudicious
use of antibiotics contributes to the current increase
in drug resistance among respiratory pathogens.5 In
addition to the development of resistant microorgan-
isms, other potential issues with antibiotics include,

allergic reactions, destruction of beneficial bowel
flora, immune suppression, overgrowth of Candida
albicans, nutrient loss and resulting deficiency state
due to diarrhea, and the cost of antibiotic therapy.6
Throughout this report, sinusitis and rhinosi-
nusitis will be used interchangeably as inflammation
of the paranasal sinuses is naturally accompanied by
inflammation of the nasal mucosa. This article will
provide useful information regarding the clinical di-
agnosis of infectious sinusitis as well as describe
symptoms, common causative organisms, and predis-
posing factors. Finally, using primary literature, this
article will underscore the management of infectious
acute sinusitis including a clinical summary table.

Classification of infectious sinusitis is based
on duration of symptoms, the specific sinus involved,
or both. Sinuses are air-filled cavities lined with
both pseudostratified and ciliated columnar epithe-
lium. Pathogens are eliminated by a natural defense
system via a mucociliary clearance that relies on
functional mucous and ciliary activity.7 The 4 para-
nasal sinuses include the frontal sinus, the ethmoid
sinuses, the maxillary sinus, and the sphenoid sinus.
Sinusitis is characterized by inflammation of, most
commonly, the maxillary and ethmoid sinuses.5 Si-


t* '

PharmaNote Volume 23, Issue 12 September 2008



Volume 23, Issue 12 September 2008


nusitis is characterized as acute with symptoms that
last less than 4 weeks, as subacute with symptoms
that last 4 8 weeks, or as chronic when symptoms
last longer than 8 weeks. All types of sinusitis have
similar symptoms and are often difficult to distin-
guish. Recurrent sinusitis is defined as having 3 or
more acute episodes a year. In contrast to acute si-
nusitis, most chronic sinusitis may be thought of as
an inflammatory disease. Notable nonspecific
symptoms of sinusitis include purulent rhinorrhea,
facial-dental pain, postnasal drainage, and nasal con-
gestion.1 Malaise, headache, fever and possibly a
cough may also accompany sinusitis.8
Symptoms of sinusitis are often vague and
clinical diagnosis is frequently rooted in subjective
findings. However, diagnosis can be confirmed with
certain imaging techniques, in combination with a
clinical history, physical examination, and/or labora-
tory tests. Computer tomography (CT) is the gold
standard of imaging techniques because it can detect
abnormalities in both the ostiomeatal complex and
the paranasal sinus cavities.1 The ostiomeatal com-
plex (OMC) is a narrow drainage pathway positioned
in the middle meatus, which allows ventilation of the
anterior ethmoid, frontal, and maxillary sinuses.7
Maxillary sinus aspiration is the best means to inden-
tify the pathological organism causing the sinusitis.7
Some predisposing factors for infectious sinusitis
include viral infections, both allergic and nonallergic
rhinitis, gastroesophageal reflux disease (GERD),
immunodeficiency, cystic fibrosis, and cilliary dys-
Common causative organisms of infectious
sinusitis include viruses and bacteria. The rhinovi-
rus, influenza virus, and parainfluenza virus are the
most common viral pathogens.1 This suggests that
an annual flu vaccine could prevent some cases of
infectious sinusitis. Also, widespread use of conju-
gate pneumococcal vaccine has led to decreasing in-
cidence of acute bacterial rhinosinusitis.4 If culture
results are unavailable, the antibiotic should target
the most common bacterial pathogen which include
Streptococcus pneumoniae, Haemophilus influenza,
Moraxella catarrhalis. Other possible bacterial
pathogens include anaerobic bacteria, Staphylococ-
cus aureus, and gram-negative bacteria.1 Antibiotics
are primary therapy for bacterial sinusitis accounting
for 21% of antibiotics prescribed for adults.9 Antibi-
otic selection should take into account geographical
prevalence of resistance patterns, predicted efficacy,

cost, side effects and bacterial cultures to streamline
therapy. However, an exact diagnosis would require
a sample of the pathogen from the paranasal sinuses,
which may not be feasible.10

Eight of the ten trials, all with a double-blind
design, included a total of 2466 participants evaluat-
ing antibiotic treatment compared to placebo for in-
fectious acute sinusitis (Lindbaek 1996; Hansen
2000; Kaiser 2001; De Sutter 2002; Bucher 2003;
Varonen 2003; Meltzer 2005; Merenstein 2005).11-1
Upchurch 2006 compared the efficacy and safety of
faropenem medoxomil for 7 or 10 days, with cefu-
roxime axetil for 10 days.19 Poole 2006 compared
two dosage strengths of levofloxacin. Six of the ten
trials compared amoxicillin to placebo.20 Kaiser et
al. used a predefined subgroup of patients with Strep-
tococcus pneumoniae, Haemophilus influenzae, or
Moraxella catarrhalis, resolution of symptoms by
day 7 occurred in 73% of those treated with azithro-
mycin compared with 47% of those who received
placebo (p = 0.007).13 Also, the median time before
symptom resolution in the azithromycin group was
five days compared to seven days in the placebo
group (p = 0.032)13 [see Table 1].
There is no definitive answer for the question
of whether antibiotic treatment for infectious acute
sinusitis has any clinical benefit. Four of the eight
placebo controlled trials demonstrated advantageous
results when treating with antibiotics. 11-18 The use of
a topical nasal steroid for the treatment of infectious
acute sinusitis is also controversial. Intranasal ster-
oids have both an anti-inflammatory and potential
decongestant action by inhibiting the transcription of
proinflammatory mediators and stabilizing phosphol-
ipid membranes.21 Meltzer et al. found that mome-
tasone furoate nasal spray (MFNS) 200 mcg twice
daily was significantly superior to placebo (p<0.001)
and amoxicillin (p=0.002) at improving symptoms.17
However, Williamson et al. reported that neither an
antibiotic nor a topical steroid alone or in combina-
tion was effective for acute sinusitis in the primary

Guidelines concerning the diagnosis and
management of infectious sinusitis, provided by the
American Academy of Allergy, Asthma and Immu-
nology, have been endorsed by the Centers for Dis-

PharmaNote Volume 23, Issue 12 September 2008

Volume 23, Issue 12 September 2008


Table 1. Descriptive characteristics of controlled trials for the use of antibiotics in acute sinusitis

Duration Median
Dose/ of Illness FlU Authors
Author Country N Comparator Antibiotic Dose/ of Ilness F/U Authors
Frequency Therapy Duration, (days) Conclusion
(days) (days)

Norway 130 pcb/pcn n,amox 1320mg TID,
amox 500 mg TID

Denmark 133 pcb/pcn

Switzerland 269 pcb/azith

Belgium 416 pcb/amox

Switzerland 252 pcb/amox/

pcn 1333 mg BID

azith 500 mg QD

amox 500 mg TID

amox/clav 875mg/1 25m



De Sutter



10 amox-9,

pcn (p = 0.008) and
amox (p <0.001)
30 are significantly
more effective than

pcn is more effective
than pcb (p < 0.05)
NA in the treatment of
acute maxillary si-

azith treatment is of
8 clinical benefit (p =
0.007) compared to

amox provides no
7.4 NA clinically important
benefits (p = 0.08)

amox/clav has no
4.5 NA advantage over
placebo (95% Cl:

abxs hasten symp-
7 >5 for 73% 14 tom relief in AMS
(p = 0.068)

Meltzer 14coun-
(2005) tries




981 pcb/MFNS/

USA 135 pcb/amox


amox 500 mg TID

10 7 to 28


1080 faro/cef faro,cef 300 mg QD, 7 or 10, 10
250 mg BID

USA 780 ev 500/ lev
USA 780 70

lev 750 mg QD,
500 mg QD

5, 10

MFSN 200 micro-
gram BID monother-
apy was significantly
28 more effective than
amox (p = 0.002)
or placebo
(p< 0.001)

for most patients
there was no im-
NA provement seen with
abxs over placebo
(p = NS)

7 day (95% Cl:
0.1,13.6) and 10 day
NA NA (95% Cl: 0.1,13.6)
faro were noninferior
to a 10 day cef regi-

lev 750 mg for 5
days is noninferior to
NA NA lev 500 mg for 10
days (95% Cl: -

amox = amoxicillin; azith = azithromycin; clav = clavulanate; doxy = doxycycline; pen = penicillin V; faro = faropenem medoxomil; cef= cefuroxime axetil; lev =
levofloxacin; MFNS = mometasone furoate nasal spray 200 mcg; abx = antibiotics; NA = not available; NS = not significant; AMS = acute maxillary sinusitis; pcb =


750mg BID,
Finland 150 pcb/amox/ amox, 100mg BID,
doxy/pcn doxy, pcn 1500mg BID
1500mg BID

Volume 23, Issue 12 September 2008


ease Control and Prevention, the American College
of Physicians-American Society of Internal Medi-
cine, the American Academy of Family Practice, the
American Academy of Pediatrics, and the Infectious
Diseases Society of America. These guidelines con-
clude that antibiotics should be considered in those
patients with severe signs and symptoms of sinusitis,
regardless of duration of illness.1 Amoxicillin is a
prudent initial antibiotic choice for uncomplicated
infectious acute sinusitis without a high prevalence
of beta-lactamase producing bacterial strains. These
resistant strains can be treated with amoxicillin-
potassium clavulanate that is generally effective
against most beta-lactamase-producing H. influen-
zae, M. catarrhalis, S. aureus, and anaerobic bacte-
The guidelines suggest that penicillin resis-
tant S pneumoniae can be treated by increasing the
prescribed amoxicillin dose to 90 mg/kg/day in two
divided doses (maximum dose of amoxicillin is 1
gram every 12 hours).1 Doxycycline provides
broader antibiotic coverage, including activity
against beta-lactamase-producing strains of H. influ-
enzae and M. catarrhalis.7 Cephalosporins are rou-
tinely prescribed for both acute and chronic sinusitis
and cefuroxime axetil and cefprozil, second-
generation cephalosporins have the advantage of
twice-daily dosing and enhanced activity against beta
-lactamase-producing H influenzae, M catarrhalis,

and S aureus. Third generation cephalosporins, such
as cefpodoxime axetil and cefdinir are appropriate
choices.1 Because azithromycin and clarithromycin
are weakly effective against penicilln-resistant H in-
fluenzae and Spneumoniae, the use of these antibiot-
ics may lead to increasing resistance to macrolides.1
Varonen et al. recommend macrolides only as second
-line drugs for acute maxillary sinusitis.16 Even
though fluoroquinolones offer broad spectrum antim-
icrobial coverage and are indicated for acute sinusi-
tis, Karageorgopoulos et al. demonstrated that when
treating acute infectious sinusitis, newer fluoroqui-
nolones confer no benefit over beta-lactam antibiot-
ics.22 An overview of available antibiotics and their
recommended doses can be found in Table 2.
The role of antibiotics in the management of
acute sinusitis is controversial.21 Also, the appropri-
ate duration of therapy is not well defined. Poole et
al. suggest that a shorter 5 day course of levofloxacin
750 mg is noninferior to a 10 day course oflevoflox-
acin 500 mg.20
As adjuvant therapy, it is reasonable to con-
sider using nasal corticosteroids to decrease the in-
flammatory response in sinusitis.1 Nasal deconges-
tants may provide temporary relief of nasal conges-
tion by constricting the sinusoids, both regulated by
alpha and alpha2 adrenoreceptors in the nasal mu-
cosa. The nasal mucosal blood flow is not signifi-
cantly affected by the alpha agonists, but studies

Table 2. Antibiotics commonly prescribed for sinusitis


Recommended Adult Dosage for ABS

Amoxicillin (Amoxil)

Amoxicillin/potassium clavulanate (A.\Ligniinc i1i )

500 mg bid
500 mg 875 mg bid

Azithromycin (Zithromax")
Cefdinir (O)1 iiccl )
Cefpdoxime (Vantin)
Cefprozil (Cefzil)
Cefuroxime (Ceftin)
Clarithromycin (Biaxin)
Clindamycin (Cleocin)
Doxycycline (Adoxa)
Gatifloxacin (Tequin)
Levofloxacin (Levaquin)

500 mg qd on day 1, then 250 mg qd on days 2-5

300 mg bid
200 mg bid

250 mg 500 mg bid

250 mg bid
500 mg bid

150 mg 450 mg qid
100 mg 200 mg qd

400 mg qd
500 mg qd

PharmaNote Volume 23, Issue 12 September 2008

Volume 23, Issue 12 September 2008


Table 3. Topical Vasoconstrictors for Decongestion of the Nasal Mucosa

Vasoconstrictors Adrenoceptor Onset Duration of action
Vasoconstrictors Dosage
Activity (minutes) (hours)

Sympathomimetic amines
Sympathomimetic amines A2 to 3 sprays in each nos-
Phenylephrine Alpha 1 to 3 1 to 4l
(NeoSynephrine) trial q3-4 hours
(Neo-Synephrine )

Imidasoline derivatives
Sidasoline derivative to 2 sprays in each nos-
Naphazoline Alpha2 1 to 3 2 to 6
(Naphcazoline Ap tril no more than q6 hours
(Naphcon Forte')

(Afrin 2-Hour) Alpha2 1to 3 5 to 12 2 to 3 sprays bid

Xylometazoline 2 to 3 drops or 2 to 3
(Otrivin ) sprays q8-10 hours
Adapted from Fagnan L.J.24

suggest that oxymetazoline, a selective alpha2 adre-
noreceptor agonist, interferes with the healing of
maxillary sinusitis by decreasing nasal mucosal
blood flow.23 As a result, alpha1 agonists, such as
phenylephrine, are the preferred topical mucosal de-
congestants. Because of the risk of rebound conges-
tion rhinitiss medicamentosa), the use of topical na-
sal decongestants should be restricted to no more
than three or four days of continuous use. In addi-
tion to alpha-adrenergic decongestants for sympto-
matic relief, other therapies include antihistamines,
glucocorticosteroids and adjunctive therapies such as
saline, mucolytics, and expectorants.1 An overview
of non-antibiotic treatment options can be found in
Table 3.

Although the role of antimicrobials in the manage-
ment of infectious sinusitis is controversial, antibiot-
ics are the primary therapy for infectious sinusitis.
Treatment suggestions for acute infectious sinusitis
are divided and vary from only treating patients with
severe or persistent symptoms with narrow spectrum
antibiotics to treating all patients with broad spec-
trum antibiotics. The purpose of antibiotics is to de-
crease symptoms and restore the sinuses to their nor-
mal function. Unnecessary antibiotic prescriptions
should be avoided and clinicians need to evaluate the
moderate benefits of antibiotic treatment against the
potential adverse effects. The most common bacte-
rial pathogens include S pneumoniae, H influenzae,

and M catarrhalis. Acute bacterial sinusitis usually
occurs following an upper respiratory infection that
results in obstruction of the osteomeatal complex,
impaired mucociliary clearance and overproduction
of secretions. In summary, antibiotic treatment for
infectious sinusitis may be effective. The guidelines
recommend that antibiotics should be prescribed for
10 to 14 days, or 7 days after the patient is symptom
free. If symptoms fail to improve in two to three
days, it is rational to switch to a second line antibi-

1. Slavin RG, Spector SL, Bernstein IL, et al. The diag-
nosis and management of sinusitis: A practice pa-
rameter update. American Academy of Allergy,
Asthma, and Immunology 2005;116:S13-47.
2. Ahovuo-Saloranta A, Borisenko OV, Kovanen N, et
al. Antibiotics for acute maxillary sinusitis (Review).
2008 The Cochrane Collaboration.
3. Pearlman AN, Conley DB. Review of current guide-
lines related to the diagnosis and treatment of rhinosi-
nusitis. Current Opinion in Otolaryngology & Head
and Neck Surgery 2008; 16:226-30.
4. Benninger MS. Acute bacterial rhinosinusitis and oti-
tis media: Changes in pathogenicity following wide-
spread use of pneumococcal conjugate vaccine. Oto-
laryngology-Head and Neck Surgery 2008; 138:274-8.
5. Small CB, Bachert C, Lund VJ, et al. Judicious Anti-
biotic Use and Intranasal Corticosteroids in Acute
Rhinosinusitis. The American Journal of Medicine
2007; 120:289-294.
6. Wilson L. Beyond Antibiotics. http//

PharmaNote Volume 23, Issue 12 September 2008

Volume 23, Issue 12 September 2008


www.drlwilson.com/Articles/antibiotics.htm. Revised
Dec 2007. Accessed July 16, 2008.
7. Leung RS, Katial R. The Diagnosis and Management
of Acute and Chronic Sinusitis. Prim Care Clin Office
Pract 2008;35:11-24.
8. Masood A, Moumoulidis L, Panesar J. Acute rhinosi-
nusitis in adults: an update on current management.
Postgrad Med. J. 2007;83:402-8.
9. Rosenfeld RM, Singer M, Jones S. Systematic review
of antimicrobial therapy in patients with acute rhinos-
inusitis. American Academy of Otolaryngology-Head
and Neck Surgery Foundation 2007;137:S32-S45.
10. Varonen H, Rautakorpi U, Nyberg S, et al. Imple-
menting guidelines on acute maxillary sinusitis in
general practice-a randomized controlled trial. Fam.
Pract 2007;24:201-6.
11. Lindbaek M, Hjortdahl P, Johnsen UL. Randomised,
double blind, placebo controlled trial of penicillin V
and amoxicillin in treatment of acute sinus infections
in adults. BMJ 1996;313:325-9.
12. Hansen JG, Schmidt H, Grinsted P. Randomised,
double-blind, placebo controlled trial of penicillin V
in the treatment of acute maxillary sinusitis in
adults in general practice. Scand J Prim Health Care
2000;18:44 -7.
13. Kaiser L, Morabia A, Stalder H, et al. Role of naso-
pharyngeal culture in antibiotic prescription for pa-
tients with common cold or acute sinusitis. Eur J Clin
Microbiol Infect Dis 2001;20:445-51.
14. De Sutter AI, de Meyere MJ, Christiaens TC, et al.
Does amoxicillin improve outcomes in patients with
purulent rhinorrhea? A pragmatic, randomized double
-blind controlled trial in family practice. J Fam Pract
2002;51:317- 23.
15. Bucher HC, Tschudi P, Young J, et al. Effect of
amoxicillin/clavulanate in clinically diagnosed acute
rhinosinusitis: a placebo-controlled, double-blind,
randomized trial in general practice. Arch Intern Med
2003;163:1793- 8.
16. Varonen H, Kunnamo I, Savolainen S, et al. Treat-
ment of acute rhinosinusitis diagnosed by clinical cri-
teria or ultrasound in primary care. A placebo-
controlled randomized trial. Scand J Prim Health Care
2003;21:121- 6.
17. Meltzer EO, Bachert C, Staudinger H. Treating acute
rhinosinusitis: comparing the efficacy and safety of
mometasone furoate nasal spray, amoxicillin, and
placebo. J Allergy Clin Immunol 2005;116:1289 -95.
18. Merenstein D, Whittaker C, Chadwell T, et al. Are
antibiotics beneficial for patients with sinusitis com-
plaints? A randomized doubleblind clinical trial. J
Fam Pract 2005;54:144 -51.
19. Upchurch J, Rosemore M, Tosiello R, et al. Random-
ized double-blind study comparing 7- and 10-day
regimens of faropenem medoxomil with a 10-day ce-

furoxime axetil regimen for treatment of acute bacte-
rial sinusitis. Otolaryngology-Head and Neck Surgery
20. Poole M, Anon J, Pagila M, et al. A Trial of High-
Dose, Short-Course Levofloxacin for the Treatment
of Acute Bacterial Sinusitis. Otolaryngology-Head
and Neck Surgery 2006;134:10-17.
21. Williamson I, Rumsby K, Benge S, et al. Antibiotics
and Topical Nasal Steroid for Treatment of Acute
Maxillary Sinusitis. JAMA 2007;298(21):2487-96.
22. Karageorgopoulos DE, Giannopoulou KP, Gram-
matikos AP, et al. Fluoroquinolones compared with
beta-lactam antibiotics for the treatment of acute bac-
terial sinusitis: a meta-analysis of randomized con-
trolled trials. Canadian Medical Association 2008;178
23. Wiklund L, Stiema P, Berglund R, Westrin KM, Ton-
nesson M. The efficacy of oxymetazoline adminis-
tered with a nasal bellows container and combined
with oral phenoxymethyl-penicillin in the treatment
of acute maxillary sinusitis. Acta Otolaryngol Suppl
24. Fagnan LJ. Acute Sinusitis: A Cost-Effective Ap-
proach to Diagnosis and Treatment. Family Physi-
cians 1998;58:8-16.

I V 3 1 m

The PharmaNote is Published by:
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Services, UF Family Practice Medical
Group, Departments of Community
Health and Family Medicine and
Pharmacy Practice
University of Florida

John G. Gums Editor

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Steven M. Smith Assistant Editor

Volume 23, Issue 12 September 2008


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