CLINICAL CROSSROADS
CONFERENCES WITH PATIENTS AND DOCTORS
A 51-Year-Old Woman With Acute Onset
of Facial Pressure, Rhinorrhea, and Tooth Pain
Review of Acute Rhinosinusitis
Peter H. Hwang, MD, Discussant
DR REYNOLDS: Mrs D is a 51-year-old woman with a history
of seasonal allergies who presented with 5 days of upper res-
piratory tract infection symptoms and facial pain.
Mrs D is in good health but has been spending time in a
large medical center recently, visiting her husband, who is un-
dergoing chemotherapy. About 5 days before presentation, she
noticed the onset of watery eyes, sneezing, chest congestion,
nasal mucus production, and myalgias. She thought she had
a cold. After a few days she began having pain in her left fore-
head, under her eye, and near her left upper teeth (she does
not have dental problems). She did not have a cough or fe-
ver. Her nasal discharge, initially clear, became green. She was
concerned about transmitting a sinus infection to her immu-
nocompromised husband. She did not take any over-the-
counter medications for her symptoms.
Mrs D has a history of seasonal allergies. She previously
saw an allergist who prescribed several years of injections;
she then took prescription allergy medication but stopped
2 years ago. She now uses nonprescription loratadine as
needed during the allergy season. She typically does not get
allergy symptoms during the winter.
Mrs D has had a number of sinus infections diagnosed
and treated with antibiotics over the years, the last occur-
ring approximately 2 years ago. She has always been pre-
scribed antibiotics when she has presented with these symp-
toms in the past.
Mrs D’s medical history is significant for hypertension, os-
teoarthritis, and a partial nephrectomy for a benign tumor. Her
medications include atenolol, hydrochlorothiazide, raniti-
dine, and glucosamine and chondroitin. Mrs D moved to the
United States in the 1970s from Haiti. She has 3 grown, healthy
children; she does not smoke tobacco, drink alcohol, or use
recreational drugs. She has commercial medical insurance.
See also Patient Page.
CME available online at www.jamaarchivescme.com
and questions on p 1833.
1798 JAMA, May 6, 2009—Vol 301, No. 17 (Reprinted)
CLINICIAN’S CORNER
Acute rhinosinusitis is a common ailment accounting for mil-
lions of office visits annually, including that of Mrs D, a 51-
year-old woman presenting with 5 days of upper respira-
tory illness and facial pain. Her case is used to review the
diagnosis and treatment of acute rhinosinusitis. Acute vi-
ral rhinosinusitis can be difficult to distinguish from acute
bacterial rhinosinusitis, especially during the first 10 days
of symptoms. Evidence-based clinical practice guidelines de-
veloped to guide diagnosis and treatment of acute viral and
bacterialrhinosinusitisrecommendthatthediagnosisofacute
rhinosinusitis be based on the presence of “cardinal symp-
toms” of purulent rhinorrhea and either facial pressure or
nasal obstruction of less than 4 weeks’ duration. Antibiotic
treatment generally can be withheld during the first 10 days
of symptoms for mild to moderate cases, given the likeli-
hood of acute viral rhinosinusitis or of spontaneously resolv-
ing acute bacterial rhinosinusitis. After 10 days, the likeli-
hood of acute bacterial rhinosinusitis increases, and initia-
tion of antibiotic therapy is supported by practice guidelines.
Complications of sinusitis, though rare, can be serious and
require early recognition and treatment.
JAMA. 2009;301(17):1798-1807 www.jama.com
On physical examination, Mrs D had a blood pressure of
138/78 mm Hg and a temperature of 96.0°F (35.6°C). She
looked well and was in no acute distress. Her conjunctivae
This conference took place at the Medicine Grand Rounds at Beth Israel Deacon-
ess Medical Center, Boston, Massachusetts, on January 31, 2008.
Author Affiliations: Dr Hwang is Associate Professor, Department of Otolaryngology–
Head and Neck Surgery, Stanford University School of Medicine, Director, Stan-
ford Sinus Center, and Director, Fellowship in Rhinology and Sinus Surgery, De-
partment of Otolaryngology–Head and Neck Surgery, Stanford University Medical
Center, Stanford, California.
Corresponding Author: Peter H. Hwang, MD, Department of Otolaryngology, 801
Welch Rd, Stanford, CA 94305 (phwang@ohns.stanford.edu).
Clinical Crossroads at Beth Israel Deaconess Medical Center is produced and ed-
ited by Risa B. Burns, MD, series editor; Tom Delbanco, MD, Howard Libman, MD,
Eileen E. Reynolds, MD, Amy N. Ship, MD, and Anjala V. Tess, MD.
Clinical Crossroads Section Editor: Margaret A. Winker, MD, Deputy Editor.
©2009 American Medical Association. All rights reserved.

were clear and without erythema. She had tenderness on
palpation over the left frontal and maxillary sinuses but no
pain on palpation over her teeth and gums. She had mini-
mal swelling below her left lower eyelid. Her nasal exami-
nation showed white rhinorrhea. Her pharynx did not show
erythema. Her lungs were clear and her cardiovascular ex-
amination results were normal.
MRS D: HER VIEW
About a week ago, I was having a headache, felt very tired,
and thought I was coming down with something, but I didn’t
know what it was. On Sunday I woke up with stuffy nose
and watery eyes; headaches again. I felt like I had tooth-
ache. And I thought, no, I know it’s not a toothache, I don’t
have anything wrong with my teeth. So I thought it must
be a sinus infection that I’m coming down with.
It was hurting on the whole side of my face, and then I
could see the puffiness under my eyes. It’s like I’m almost
deaf in one ear. Talking on the phone, I can hardly hear what
the other person is saying. That’s how bad it can get.
What was coming out of my nose was clear at first, then
after a few days it started to have a greenish color. That’s
when I thought, definitely, it’s a sinus infection, and I need
medical attention.
In the past, when I had sinus infections, it usually hap-
pened when I was at work. I couldn’t concentrate at all, be-
cause my head felt like it was going to explode any minute.
But lately it’s been different symptoms. Basically, you can
mistake it for a cold, or you might even think it’s allergies
because it starts with itchy eyes, itchy throat.
Allergies are usually temporary. I could go to bed with
itchy eyes or an itchy throat, and by next morning it’s gone,
so I know it’s allergies. A sinus infection lasts a long time.
I’m used to having sinus infections and I know when I
have one. I had one 2 years ago. So on my way to the doc-
tor, I knew I was going to ask for antibiotics, because there’s
no way I can treat this without having medication. With that
type of sinus infection, I don’t think [pseudoephedrine hy-
drochloride] or anything over the counter would have helped
me. That’s my own opinion, my situation.
I would like to know what the difference is between a com-
mon cold and a sinus infection. Where does a sinus infec-
tion come from? How do you get it? What triggers it?
QUESTIONS FOR DR HWANG
How can a physician diagnose acute rhinosinusitis based on
patient history and physical examination? What is the mi-
crobiology of acute sinusitis? What are the indications, if
any, for imaging or endoscopy in patients with symptoms
of acute sinusitis? How effective are antibiotics in the treat-
ment of acute rhinosinusitis and what regimens, if any, do
you recommend for first-line treatment? What nonphar-
macological treatments are effective? What complications
of acute rhinosinusitis should primary care physicians look
for? What do you recommend for Mrs D?
©2009 American Medical Association. All rights reserved.
CLINICAL CROSSROADS
DR HWANG: Acute rhinosinusitis is defined as sympto-
matic inflammation of the mucosa of the nasal cavity and
paranasal sinuses lasting less than 4 weeks in duration. Be-
cause the inflammatory condition almost always extends be-
yond the sinus cavities to involve the nasal cavity as well,1,2
the term rhinosinusitis is preferred to sinusitis.
Each year, more than 20 million US adults are diagnosed as
having acute bacterial rhinosinusitis.3 The diagnosis and treat-
ment of rhinosinusitis account for an estimated $5.8 billion per
year in direct medical expenditures, $3 billion of which is spent
on acute bacterial rhinosinusitis.3,4 The socioeconomic impact
of rhinosinusitis is even greater when considering indirect costs
from decreased work productivity and missed work days, in
addition to global impairment of quality of life.
The paranasal sinuses—maxillary, ethmoid, sphenoid, and
frontal—are 4 paired air-filled spaces located between the or-
bits and below the anterior cranial fossa. They are lined with
ciliated, secretory respiratory mucosa. The sinuses drain
through narrow ostia several millimeters in diameter and are
prone to obstruction when the mucosal lining swells in re-
sponse to viral infection or environmental irritation (FIGURE 1).
Diagnosis
The diagnosis of acute rhinosinusitis is based primarily on
medical history and is supported secondarily by confirma-
tory physical findings. In 2007, an updated clinical prac-
tice guideline was developed by a multidisciplinary expert
panel based on evidence from the literature.5 The guide-
line proposes that a diagnosis of acute rhinosinusitis should
be based on presence of 2 cardinal symptoms: purulent rhi-
norrhea and either facial pressure or nasal obstruction. Other
suggestive signs and symptoms (though not required for the
diagnosis) include headache, fever, fatigue, maxillary den-
tal pain, cough, hyposmia or anosmia, and ear pressure or
fullness. Although the sensitivity and specificity of this al-
gorithm for the diagnosis of acute sinusitis has not been stud-
ied, earlier studies have determined the sensitivity and speci-
ficity of the individual cardinal symptoms for a diagnosis
of acute sinusitis: purulent rhinorrhea has a sensitivity of
72% and a specificity of 52%; facial pressure has a sensitiv-
ity of 52% and a specificity of 48%; and nasal obstruction
has a sensitivity of 41% and a specificity of 80%.6
Anterior rhinoscopy, performed with a handheld oto-
scope or fiber-optic nasal endoscope, may reveal diffuse mu-
cosal edema, inferior turbinate hypertrophy, and copious
rhinorrhea (FIGURE 2). Facial tenderness and oropharyn-
geal discharge may also be supportive of a diagnosis of acute
rhinosinusitis. Notably, the aforementioned diagnostic cri-
teria apply to both viral and bacterial rhinosinusitis and do
not distinguish between them. The guidelines propose, based
on expert consensus, that the duration of acute rhinosinu-
sitis is expected to be less than 4 weeks.1
The first step in evaluation of Mrs D is determining whether
she has acute rhinosinusitis, irrespective of either viral or bac-
terial etiology. Mrs D describes symptoms of purulent rhinor-
(Reprinted) JAMA, May 6, 2009—Vol 301, No. 17 1799
CLINICAL CROSSROADS

rhea, facial pressure, and nasal obstruction, satisfying the cri-
teria for cardinal symptoms. She also reports multiple second-
ary criteria, including headache, fatigue, dental sensitivity, and
ear fullness. The duration of her symptoms is less than 4 weeks.
Although she has a history of nasal allergies, her current symp-
toms of purulent rhinorrhea and facial pain are not consistent
with allergic rhinitis, which would be expected to manifest as
clear rhinorrhea, sneezing, and nasal pruritus.7 Physical exami-
nation findings such as facial tenderness to palpation or tym-
panic membrane retraction may support a diagnosis of sinus-
itis but are not required, although in her case, ear examination
to assess her reports of ear fullness would be appropriate. There-
fore, on the basis of history it is reasonable to diagnose Mrs D
as having acute rhinosinusitis.
Determining whether Mrs D has viral vs bacterial rhino-
sinusitis is a more complex matter. The most common form
of acute rhinosinusitis is acute viral rhinosinusitis (AVRS). More
than 1 billion viral upper respiratory tract infections are esti-
mated to occur each year in the United States, and an esti-
mated 39% to 87% of upper respiratory tract infections are
estimated to result in acute viral rhinosinusitis.8,9 Acute viral
rhinosinusitis, a typically self-limited illness, may be clini-
cally indistinguishable from upper respiratory tract infec-
tions without sinusitis. Upper respiratory tract infection is a
primary risk factor for the development of acute bacterial rhino-
sinusitis (ABRS), with approximately 0.5% to 2% of upper res-
piratory tract infections progressing to bacterial infection.10
Acute bacterial rhinosinusitis is also largely a self-limited ill-
ness, with a 40% to 60% rate of spontaneous resolution, based
on systematic review of placebo-controlled clinical trials.5 How-
ever, antibiotic therapy in patients with ABRS can shorten the
duration of symptoms; a meta-analysis of 16 randomized con-
trolled trials in ABRS showed that antibiotics conferred a higher
rate of partial or complete resolution of acute rhinosinusitis
symptoms compared with placebo, with an odds ratio of 1.64
(95% confidence interval, 1.35-2.00).11 The meta-analysis did
not detect a benefit from antibiotics in the prevention of sup-
purative complications (orbital, intracranial extension), but
given the rare incidence of complications, the meta-analysis
may have been limited by sample size.
Since viral and bacterial rhinosinusitis can overlap in clini-
cal presentation, it may be difficult to discern viral from bac-

Figure 1. Anatomy of Paranasal Sinuses and Nasal Passages

L AT E R A L V I E W

CORONAL SECTION

Ethmoid sinus Frontal sinus

Normal Acute rhinosinusitis

Sphenoid sinus VIEW

Frontal sinuses

Maxillary sinus

ORBIT
Ethmoid sinuses

Middle turbinate Edematous

mucosal lining

PA R A S A G I T TA L S E C T I O N Middle meatus

Frontal sinus

Patent Blocked
Sphenoid sinus Superior ostium ostium
turbinate
MAXILLARY MUCUS
SINUS
Mi
Middle
VIEW tur
turbinate

Middle meatus
Mi
Nasal septum
Inferior turbinate

IInferior
f
turbinate
Orifice of
eustachian tube

The parasagittal view demonstrates mucociliary drainage patterns of the paranasal sinuses.

1800 JAMA, May 6, 2009—Vol 301, No. 17 (Reprinted) ©2009 American Medical Association. All rights reserved.

Figure 2. Endoscopic Views of the Middle Meatus
Angle and field of nasal endoscopic view A Normal
Nasal
septum
Lateral
L Middle
n
nasal wall
Middle
te
e
turbinate
Middle meatus
Middle meatus
See video at http://www.jama.com/cgi/content/full/301/17/1798/DC1.
terial etiologies. In the first 5 days of illness, AVRS and ABRS
maybeindistinguishable.Thediagnosticdistinctionisthusmade
based on duration and progression of symptoms.5 The expected
clinical course of AVRS is marked by resolution of symptoms
within 10 days following the onset of an upper respiratory tract
infection, whereas ABRS is presumed when acute symptoms
persist for 10 days or more. Acute bacterial rhinosinusitis may
also be diagnosed if the acute symptom complex exists for less
than 10 days but demonstrates clinical worsening after initial
improvement.5 The presence of “double worsening” carries a
likelihood ratio of 2.1 for a diagnosis of ABRS, based on a ref-
erence standard of a sinus computed tomography (CT) scan.12
Because Mrs D’s symptoms have been present for 5 days
and the temporal cut point for distinguishing viral from bac-
terial sinusitis is 10 days, it cannot be determined with cer-
tainty whether Mrs D’s symptoms represent true bacterial
rhinosinusitis.
Microbiology
The most common viruses implicated in AVRS, as deter-
mined by maxillary sinus puncture and aspiration in an out-
patient setting, are rhinovirus, adenovirus, influenza virus,
and parainfluenza virus.13,14 Owing to a paucity of studies,
the relative incidence of each virus in AVRS is not well char-
acterized. The most common pathogens associated with ABRS
are Streptococcus pneumoniae (33%), Haemophilus influen-
zae (32%), Staphylococcus aureus (10%), and Moraxella ca-
tarrhalis (9%).15 In approximately one-quarter of cases, 2
distinct pathogens may be isolated.16 Since the introduc-
tion of the 7-valent pneumococcal vaccine for children, there
appears to be a trend toward decreasing S pneumoniae iso-
lates and increasing prevalence of H influenzae isolates de-
rived from adults with acute maxillary sinusitis.17
In clinical practice, viral culture of nasal secretions is not rec-
ommended for routine cases, given the self-limited nature of
©2009 American Medical Association. All rights reserved.
CLINICAL CROSSROADS
B Acute rhinosinusitis
Lateral nasal wall Lateral nasal wall
Nasal
septum
Middle
turbinate
turbinate
Middle meatus
(filled with pus)
AVRS. Bacterial culture of purulent secretions may be indicated
when there is concern regarding resistant pathogens, such as
incasesthatarerefractorytoprimaryantibiotictherapy,orthose
involving an immunocompromised host.18 When cultures are
deemed necessary, a referral to an otolaryngologist is appro-
priate, as culture methods can significantly affect the yield. The
gold standard for sinus culture technique is antral puncture and
aspiration, which requires a large-bore trocar or needle to be
passed through the canine fossa or inferior meatus. Antral punc-
ture may not be practical for routine culture given the morbid-
ityoftheprocedure,whichincludesdentalorfacialpain,bleeding,
facial swelling, and false passage of the trocar.19,20 An excellent
alternative to antral puncture is transnasal endoscopic culture,
which can be readily performed without significant morbid-
ity in the otolaryngologist’s office using a topical anesthetic.20
Endoscopically guided middle meatal cultures have a satisfac-
tory yield and show excellent correlation with antral aspi-
ration.20-22 In a meta-analysis of 126 patients,22 the yield of endo-
scopic middle meatal cultures was assessed against the gold
standard of maxillary sinus puncture and aspiration performed
in the same patient (131 culture pairs). Endoscopic culture had
a sensitivity of 80.9%, a specificity of 90.5%, a positive predic-
tive value of 82.6%, a negative predictive value of 89.4%, and
an overall accuracy of 87.0%.
At the time of nasal endoscopy, the otolaryngologist can
also perform a more detailed examination of the nasal
anatomy to identify potential predisposing anatomic fac-
tors such as nasal polyps, septal deviation, or nasal masses.
Simple blind swabs of the nasal cavity are likely to be con-
taminated by normal colonizing bacteria of the nasal vesti-
bule and should not be performed.23,24
Since Mrs D has had uncomplicated symptoms for only 5
days, there is no role for endoscopic culture in her case. How-
ever, if her symptoms persisted for 10 days and she subse-
quently failed a course of antibiotic therapy, referral for en-
(Reprinted) JAMA, May 6, 2009—Vol 301, No. 17 1801
CLINICAL CROSSROADS

doscopic sinus cultures would potentially be indicated. In
addition, if she were immunocompromised or if an extrasi-
nus complication were suspected, referral to an otolaryngolo-
gist would also be indicated.23
Radiologic Studies
Mrs D did not have any radiographic imaging during this acute
episode. Radiographic imaging is generally not indicated in the
evaluation of routine uncomplicated acute rhinosinusitis.5 If
pursued, plain sinus radiography may provide satisfactory im-
agesofthemaxillarysinus,andithasmoderatesensitivity(73%)
and specificity (80%) for predicting positive antral puncture
results.25 Imaging of the ethmoid, frontal, and sphenoid sinuses
offers lower sensitivity and specificity owing to radiologic ar-
tifact. Ultrasonography offers uneven diagnostic accuracy be-
cause of operator-dependent factors and is therefore not rec-
ommendedforroutineimaging.25 Computedtomographyscans
offer improved bony and soft tissue detail, but in the context
of acute rhinosinusitis, CT scans may reveal sinus fluid levels
in patients with AVRS as well as those with ABRS (FIGURE 3).
Since CT scans cannot distinguish between viral and bacte-
rial etiologies, their utility in evaluating acute rhinosinusi-
tis is limited. In a study by Gwaltney et al,9 31 healthy par-
ticipants who developed AVRS after controlled inoculation
demonstrated an 87% mucosal thickening or air-fluid levels
of the maxillary sinuses on CT scan. Abnormalities were also
documented on CT in the ethmoid, frontal, and sphenoid si-
nuses in 65%, 32%, and 39%, respectively. After 2 weeks, 79%
of the CT abnormalities had cleared. Other studies have shown
that radiologic evidence of mucosal abnormality may be ob-
served in as much as 42% of asymptomatic healthy individu-
als26,27; thus, the significance of a positive CT result must be
considered in the appropriate clinical context.
Imaging studies are indicated in the evaluation of pa-
tients with a suspected complication of ABRS, such as those
presenting with diminished visual acuity, diplopia, perior-
bital edema, severe headache, or altered mental status.5 Com-
puted tomography with contrast is the diagnostic study of
choice for the evaluation of complicated acute sinusitis that
may be extending to the dura, brain, or orbits.28,29 Mag-
netic resonance imaging is not indicated for routine evalu-
ation of ABRS but may provide complementary soft tissue
detail to CT for the evaluation of complications of acute
rhinosinusitis.28,29
Treatment
To minimize the inappropriate use of antibiotics for viral
infections, antibiotic treatment should be initiated only when
a higher likelihood of ABRS exists.30 The 10th day of symp-
toms represents the recommended cut point for initiating
antibiotic therapy because most cases of AVRS would be ex-
pected to resolve within 10 days.5 Furthermore, since 40%
to 60% of ABRS resolves spontaneously, a significant pro-
portion of patients who have true bacterial sinusitis show
evidence of symptom abatement or resolution by day 10 and
do not require antibiotics. For patients with fewer than 10
days of symptoms, observation without antibiotics is there-
fore recommended if the symptoms are mild and if clinical
severity is either stable or improving. Antibiotic treatment
is recommended within the first 10 days if patients have se-
vere symptoms or symptoms of “double worsening.” Addi-
tional consideration for earlier initiation of antibiotic treat-
ment should be given in immunocompromised hosts.5 Mrs
D was only 5 days into her course when she was evaluated;
because she is an otherwise healthy host, she did not re-
quire antibiotic therapy at this stage. She expressed con-

Figure 3. Radiologic Features of Acute Rhinosinusitis (Coronal Noncontrast Computed Tomography)

A B

A, Image demonstrates an air-fluid level in the right maxillary sinus (arrowhead) as well as partial opacification of the ethmoid sinuses bilaterally. B, Image shows
mucosal thickening of the left sphenoid sinus (arrowhead). Radiologic imaging is not routinely indicated for the diagnosis of acute rhinosinusitis.

1802 JAMA, May 6, 2009—Vol 301, No. 17 (Reprinted) ©2009 American Medical Association. All rights reserved.

cern over her infection given her husband’s immunocom-
promised state, but since her infection is most likely viral,
antibiotics still would not be indicated. She should prac-
tice careful hygiene, washing her hands frequently with soap.
For patients with 10 or more days of symptoms, clini-
cians have the option of initiating antibiotics or continuing
with watchful waiting (TABLE). If a patient has symptoms
that are mild or improving and a temperature less than
38.1°C, clinical guidelines support the option of continued
observation without antibiotics for an additional 7 days.5 The
patient may be treated with supportive care for relief of symp-
toms in lieu of antibiotics. Observation is supported as a vi-
able option by randomized controlled trials (RCTs) of an-
timicrobials vs placebo; spontaneous improvement of
community-acquired, uncomplicated rhinosinusitis may be
as high as 73% after 7 to 12 days (vs 87% with antibiotics
in the same period).31 The watchful waiting option re-
quires a reliable patient who will notify the clinician promptly
of any worsening of symptoms, at which point antibiotics
should be given. The clinician should also consider factors
such as age, immune status, and comorbidities when choos-
ing to observe patients with ABRS.
For patients with 10 or more days of persistent symp-
toms of rhinosinusitis, antibiotic therapy is equally accept-
able as is watchful waiting. Antibiotics are administered to
control infection and to secondarily reduce mucosal edema
and restore ostial patency.35 The literature regarding the ef-
ficacy of antibiotic treatment for acute rhinosinusitis is dif-
ficult to interpret because of wide variations in diagnostic
inclusion criteria. For example, an RCT by Williamson et
al36 concluded that antibiotics (alone or in combination with
Table. Summary of Best Available Evidence for Medical Therapy for Acute Rhinosinusitis a
Source Treatment Study Design
Falagas et al,11 2008 Antibiotics Meta-analysis
of placebo-
controlled RCTs
Rosenfeld et al,31 2007 Antibiotics Meta-analysis
of placebo-
controlled RCTs
Zalmanovici and Yaphe,32 Topical nasal Meta-analysis
2007 corticosteroids of placebo-
controlled RCTs
Braun et al,33 1997 Antihistamines Placebo-
controlled RCTs
Rabago et al,34 2002 Saline irrigations RCT with
nontreatment arm
Abbreviations: CI, confidence interval; OR, odds ratio; RCT, randomized controlled trial; RD, rate difference.
a Based on systematic review. No RCTs are available studying decongestants for treatment of acute bacterial rhinosinusitis.
©2009 American Medical Association. All rights reserved.
CLINICAL CROSSROADS
nasal steroids) showed no benefit vs placebo in the treat-
ment of acute maxillary sinusitis. Participants were older
than 15 years of age and met Berg and Carenfelt diagnostic
criteria for acute maxillary sinusitis.37 However, patients had
a range of 1 to 28 days of symptoms, with a median of 7
days, and based on other studies it is likely that the RCT
included significant numbers of patients with viral rhino-
sinusitis. The subgroup of patients with a longer duration
of symptoms may have benefited from antibiotics.
Systematic reviews offer grade B evidence to support the
use of antibiotics in ABRS.11,38-43 For mild cases of ABRS, the
incremental benefit is somewhat modest. Antibiotics ap-
pear to shorten the duration of illness and may increase the
rate of cure by 15% (95% confidence interval, 4%-25%) com-
pared with placebo (35% cure for placebo at 7-12 days vs
50% for antibiotics).31 The authors calculated that 7 pa-
tients would need to be treated to achieve 1 additional posi-
tive outcome, while diarrhea and adverse events were 80%
more common in those treated with antibiotics. For mod-
erate cases, no RCTs have been published, but treatment of
moderate ABRS offers the implied benefit of reducing po-
tential complications.
When antibiotic therapy is initiated, choosing an antimi-
crobial with the narrowest spectrum against the most prob-
able pathogen is prudent to minimize the risk of cultivating
resistance. Amoxicillin (500 mg every 8 hours) is recom-
mended as first-line therapy, given its narrow spectrum, low
cost, and favorable adverse effect profile.5 Increased rates of
penicillin resistance due to penicillin-binding protein–
producing S pneumoniae have led to the use of higher dosing
regimens of amoxicillin (penicillin-binding proteins can be
Sample
Size Outcome
1813 Antibiotics were associated with a higher rate of cure (OR,
1.82; 95% CI, 1.34-2.46).
2648 Antibiotics were associated with a higher rate of cure or
improvement (OR, 1.64; 95% CI, 1.35-2.00).
1963 Antibiotics were associated with a higher rate of adverse
events (OR, 1.87; 95% CI, 1.21-2.90).
3108 Antibiotics were associated with incrementally higher cure
at 7-12 d (absolute RD, 0.15; 95% CI, 0.04-0.25).
Antibiotics were not associated with a higher rate of
cure at 3-5 d (RD, 0.01; 95% CI, −0.02 to 0.05).
Antibiotics were not associated with a higher rate of
cure at 14-15 d (RD, 0.04; 95% CI, −0.02 to 0.11)
1943 Topical nasal steroids were associated with a higher rate of
improvement or cure (relative risk, 1.11; 95% CI,
1.04-1.18) (RD, 0.07; 95% CI, 0.03-0.11).
139 In atopic patients with acute rhinosinusitis, loratadine
significantly reduced sneezing (P = .003) after 14 d and
nasal obstruction (P = .002) after 28 d. No nonatopic
patients studied.
76 Daily irrigation with hypertonic saline improved disease-
specific quality-of-life measure at 3 mo (P ⬍ .001) and 6
mo (P ⬍ .001) in a mixed population of patients with
recurrent acute sinusitis and chronic sinusitis.
(Reprinted) JAMA, May 6, 2009—Vol 301, No. 17 1803
CLINICAL CROSSROADS
overcome by the use of amoxicillin instead of penicillin). How-
ever, ␤-lactamase−producing M catarrhalis and H influenzae
cannot be overcome by higher dosing and may require com-
bination therapy with clavulanic acid or a change in class of
antimicrobial. Resistance rates vary regionally and range from
12% to 31% for intermediate or highly resistant S pneumo-
niae; 30% to 40% for H influenzae; and ⱖ90% for M catarrha-
lis.3,44,45 The increasing incidence of methicillin-resistant S au-
reus is also of concern (69% incidence among S aureus isolates
in data from 2004-2006).46 In addition, identification of ␤-
lactamase–negative ampicillin-resistant strains of H influen-
zae have been reported from Japan and Spain47,48; the mecha-
nism of resistance appears to be a mutation in penicillin-
binding proteins.49 Locoregional histograms of bacterial
resistance should be referenced to understand resistance trends
in the local community. Trimethoprim-sulfamethoxazole, mac-
rolides, and second- and third-generation oral cephalospor-
ins have also been validated by RCTs and are cost-effective,
acceptable alternative first-line therapies in penicillin-
allergic patients.3,50-55
The recommended duration of antimicrobial therapy based
on clinical guidelines is 10 days,5 based mostly on the typical
duration of therapy used in RCTs.5 However, according to a
meta-analysis of 12 RCTs,11 no statistical difference in effi-
cacy existed between short-course (3-7 days) vs long-course
(6-10 days) treatment (odds ratio, 0.95; 95% confidence in-
terval, 0.81-1.12). Adverse events were fewer in the 5- vs 10-
day course (odds ratio, 0.79; 95% confidence interval, 0.63-
0.98). This meta-analysis was limited by heterogeneity in the
entry criterion of symptom duration (any patient with symp-
toms ⬍30 days with positive radiological findings). Further-
more, there was overlap in the treatment duration of the com-
parison groups, with the long-course group including 6- and
7-day treatments and the short-course group also including
7-day treatments. The optimal duration of therapy remains
to be definitively validated by clinical trials.
Treatment failure is defined as progression of symptoms
at any time during treatment or failure to improve after 7
days of therapy.5 Patients in whom first-line therapy with
amoxicillin fails or who relapse within 6 weeks require an
alternative antibiotic with a broader spectrum. Fluoroqui-
nolones (250 mg/d) or high-dose amoxicillin-clavulanate
(4 g/d) may be considered.3 If an odontogenic source is iden-
tified, enhanced coverage of anaerobes and gram-negative
bacteria is indicated.56 For refractory cases, specialty refer-
ral to an otolaryngologist may be beneficial for obtaining
endoscopic cultures to guide therapy.
Adjunctive Therapies
A wide variety of over-the-counter remedies have been of-
fered for symptomatic relief of acute rhinosinusitis. On the
whole, no adjunctive therapy has been proven to shorten
the duration of illness. However, these treatments are gen-
erally well tolerated and may be beneficial for patients who,
like Mrs D, can be managed with watchful waiting.
1804 JAMA, May 6, 2009—Vol 301, No. 17 (Reprinted)
Decongestants. Topical decongestants such as oxymetazo-
line are more effective than oral decongestants such as pseu-
doephedrine, although both forms are likely to alleviate symp-
toms.57,58 There is grade C evidence but no RCT to support
their use.5 Patients using topical decongestants should be
cautioned against prolonged use of medication (⬎5 days)
to avoid the risk of rebound rhinitis.59
Corticosteroids. Topical nasal corticosteroids reduce in-
flammation of the nasal mucosa and may have possible ef-
ficacy in treating acute rhinosinusitis. A 2007 Cochrane re-
view supported the use of topical nasal corticosteroids as
monotherapy or adjuvant therapy to antibiotics32 based on
a meta-analysis of 4 double-blind, placebo-controlled trials.
Currently, there is no US Food and Drug Administration–
approved indication for the use of topical corticosteroids in
acute rhinosinusitis. As with the studies of antibiotics in
ABRS, published reports investigating topical corticoste-
roids should be interpreted carefully because they are often
based on heterogeneous patient populations (acute, chronic,
and/or viral rhinosinusitis) and treatment regimens (con-
comitant decongestant, saline irrigation, antibiotic). More
well-designed clinical trials are needed to definitively vali-
date the routine use of topical nasal steroids in acute rhino-
sinusitis. There is no evidence to support the routine use of
oral corticosteroids for acute rhinosinusitis.
Antihistamines. Studies evaluating the role of antihista-
mines in acute rhinosinusitis comprise only grade D evi-
dence.5 Antihistamines may have a minor role in treating atopic
patients with acute rhinosinusitis and are not indicated in nona-
topic patients.33,60 In Mrs D’s case, her symptoms are more sug-
gestive of an infectious etiology than an atopic etiology; there-
fore, antihistamines are not indicated.
Saline Irrigations. Buffered isotonic saline may be deliv-
ered to the nasal cavity by active (squeeze bottle) or pas-
sive (Neti pot) means. The mechanical cleansing of the na-
sal cavity has been shown to be beneficial in patients with
recurrent acute sinusitis, chronic rhinosinusitis, and aller-
gic rhinitis,34,61,62 but no studies have been done in patients
with ABRS alone. Clinical guidelines neither advocate nor
discount the use of irrigations.5 Given its low adverse effect
profile, saline irrigation may be beneficial for patients seek-
ing self-care options to supplement pharmacotherapy.
Complications
Complications of AVRS are uncommon, but specific rates are
difficult to quantify because many cases of AVRS do not come
to medical attention. While transient hyposmia is common
in AVRS, permanent anosmia may also occur rarely.63 Women
may be disproportionately affected by viral-induced smell dis-
turbances compared with men; women represented 67% of
patients presenting with viral-induced olfactory loss to a ma-
jor smell and taste clinic.64 The most common complication
of AVRS is secondary bacterial infection resulting in ABRS.10
Although the incidence of complications in ABRS is rare,
estimated at 1 in 1000,38 all patients with ABRS should be
©2009 American Medical Association. All rights reserved.

screened for the possibility of an underlying infectious com-
plication. Complications of ABRS may be associated with
significant morbidity or even mortality. The primary sites
involved in complicated ABRS are the orbits and central ner-
vous system, typically by direct extension (FIGURE 4). Or-
bital infections may range from preseptal cellulitis to sub-
periosteal abscess to orbital abscess, typically transmitted
from the ethmoid sinus across the medial orbital wall.65 Or-
bital extension may lead to cavernous sinus thrombosis.
Acute sphenoid sinusitis or frontal sinusitis may be associ-
ated with CNS complications ranging from meningitis to epi-
dural abscess or frank brain abscess.66 Physical findings sug-
gestive of a complication may include periorbital edema,
disconjugate gaze, disorientation, or prostration. Any pa-
tient with ABRS who presents with visual symptoms, se-
vere headache, somnolence, or high fever should be evalu-
ated radiologically with an emergent sinus CT scan with
contrast.29 While there is no indication for surgery in pa-
tients with uncomplicated ABRS, surgery may be emer-
gently indicated in patients experiencing extrasinus com-
plications of ABRS.
RECOMMENDATIONS FOR MRS D
Mrs D presents with a 5-day history of symptoms that is con-
sistent with acute rhinosinusitis. The possibility of ABRS ex-
ists, but given the relatively early stage of presentation, it is
not possible to readily distinguish between AVRS and ABRS.
Figure 4. Anatomy of the Orbital Apex and Parasellar Region
AXIAL SECTION
Orbital fat
VIEW
Nasal septum EYE
Ethmoid Medial rectus
sinuses muscle
Medial wall
of orbit
Sphenoid
sinuses
Optic nerve
Dura
Internal
carotid artery
Cavernous Pituitary gland
sinus
Complications of acute sinusitis may include extrasinus spread of infection resulting in orbital cellulitis or cavernous sinus thrombosis.
©2009 American Medical Association. All rights reserved.
CLINICAL CROSSROADS
Given that her symptoms appear to be mild to moderate in
severity, I would favor treating for 5 more days with symp-
tomatic measures, such as topical decongestant sprays, oral
decongestants, over-the-counter analgesics, and saline ir-
rigations. If she improves, the presumptive diagnosis would
be AVRS or spontaneously resolving ABRS. She should be
instructed to contact her physician in the meantime if she
develops a fever or her symptoms otherwise worsen. Par-
ticularly in light of her husband’s immunocompromised state,
she should wash her hands frequently to avoid transmit-
ting infection.
If Mrs D reached the day 10 cut point without improve-
ment in her symptoms, I would prescribe oral amoxicillin
for 10 days for presumed ABRS. I would expect near-
complete resolution by the end of the 10-day course of an-
tibiotics. If she were to have lingering or worsening symp-
toms after 10 days of amoxicillin, I would extend therapy
for an additional 10 days using amoxicillin/clavulanate or
a respiratory fluoroquinolone. At that point, I would con-
sider obtaining endoscopic cultures as well to guide therapy.
QUESTIONS AND DISCUSSION
QUESTION: A lot of patients present like this patient and say
that they’ve had multiple episodes of sinusitis and they get
better only after antibiotics. What do you tell them?
DR HWANG: It’s certainly possible that such a patient may
have true recurrent ABRS, but this diagnosis can be diffi-
VIEW CORONAL SECTION
BRAIN
Pituitary gland
Optic nerve Internal
carotid artery
Internal
carotid artery
Cranial nerves (CN)
CN III
Dura CN IV
CN VI
Cavernous
CN V1
sinus
CN V2
Sphenoid sinus
(Reprinted) JAMA, May 6, 2009—Vol 301, No. 17 1805
CLINICAL CROSSROADS
cult to distinguish from recurrent viral rhinitis or viral si-
nusitis. If a patient with recurrent viral sinusitis has re-
ceived antibiotics on the fifth day of symptoms every time
they’ve presented to their physician, then that patient might
associate the receiving of antibiotic to the resolution of their
disease. In actuality, the natural course of this patient’s dis-
ease process dictates that symptoms would have resolved
on their own regardless of antibiotic intervention.
In my practice, I would perform a nasal endoscopy to
evaluate for purulent discharge or anatomic abnormalities
that might be predisposing the patient to recurrent infec-
tions. If the endoscopy results were normal, I would en-
courage the patient to forgo antibiotics at the time of the
next exacerbation, under my close supervision. As we edu-
cate our patients about the differences between viral and bac-
terial infections, they become comfortable with the notion
of not receiving antibiotics. And while some patients will
manifest true recurrent ABRS, many patients will find that
their disease process resolves without antibiotics.
QUESTION: Are there normal bacterial flora in the si-
nuses? What are the defenses that prevent either the nor-
mal flora or other organisms from turning into a sinusitis?
Are there defensins or other local products that are se-
creted? And is there more mechanistic information about
what gets disrupted when there is a viral infection?
DR HWANG: That’s a great question. Colonizing bacteria
have been isolated from the sinuses, but we do not expect
to encounter the pathogens typically associated with ABRS,
such as S pneumoniae, H influenzae, or M catarrhalis.67 In
addition, the nasal vestibule is heavily colonized with bac-
teria. A simple nasal swab taken for the purpose of sinus
culture will likely be contaminated by vestibular flora with-
out yielding true pathogens. In contrast, an endoscopically
derived culture specifically targeting deeper areas of the nose
will have much greater yield. Thus, I recommend that all
sinus cultures be obtained endoscopically.
In terms of local defenses against infection, mucociliary
clearance is the primary macroscopic defense against par-
ticulate penetration of the sinus cavities. At a microscopic
level, the sinonasal mucosa also demonstrates innate im-
mune functions that maintain the protective barrier of the
intact epithelium. Endogenous agents such as toll-like re-
ceptors, defensins, and nitric oxide may have important lo-
cal immune functions. A viral insult may disrupt local im-
munity by overwhelming the milieu with toxic cytokines
and degranulation products of white blood cells.55 Injury
to the epithelial barrier may disrupt both ciliary function
and local immune surveillance, thereby predisposing to bac-
terial superinfection.56
QUESTION: Could you comment further about the guide-
line recommendations for amoxicillin as first-line therapy?
Would that change if the person were immunocompro-
mised or had other comorbid conditions that could com-
plicate the potential flora? There are certainly some limita-
tions to the spectrum of coverage of amoxicillin.
1806 JAMA, May 6, 2009—Vol 301, No. 17 (Reprinted)
DR HWANG: Absolutely. The recommendations discussed
today apply to immunocompetent individuals with mild to
moderate sinusitis. If you are treating a transplant patient or
a patient with diabetes with a more severe clinical presenta-
tion of acute sinusitis, it is likely that your threshold for in-
tervention will be lower. If the patient has severe symptoms,
you may not choose to wait 10 days to begin antibiotic therapy,
and I think it would be very reasonable to broaden your cov-
erage beyond amoxicillin. One may see a higher incidence
of amoxicillin-resistant organisms such as ␤-lactamase–
producing H influenzae, methicillin-resistant S aureus, or even
Pseudomonas. If you do not see a clinical response after the
first few days of therapy, you may wish to consult an otolar-
yngologist for endoscopy and culture for precise identifica-
tion of the pathogen and its antibiotic sensitivities.
Financial Disclosures: None reported.
Additional Information: Online video is available at http://www.jama.com/cgi
/content/full/301/17/1798/DC1.
Additional Contributions: We thank the patient for sharing her story and for pro-
viding permission to publish it.
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