Transcript Supplemental Content - Annals of Internal Medicine

© 2016 American College of Physicians
The information contained herein should never be
used as a substitute for clinical judgment.
BEYOND THE GUIDELINES:
Would you recommend antibiotics for this patient with
acute upper respiratory symptoms?
Medicine Grand Rounds
September 29, 2016
Discussants
BIDMC Series Editor
Moderator
Diane Brockmeyer, MD
Howard Libman, MD
Deborah Cotton, MD, MPH
Howard Gold, MD
The Series Editors have no conflicts of interest to disclose.
Conflict of Interest Disclosure
The speakers have no financial relationships
with a commercial entity producing
healthcare-related products and/or
services.
Howard Libman, MD
Deborah Cotton, MD, MPH
Diane Brockmeyer, MD
Howard Gold, MD
OUR PATIENT
• Mr. X is a 62 y.o. man with a history of recurrent sinusitis
• He takes an oral antihistamine and nasal steroids throughout
the year for allergies
• He presents complaining of a several week history of upper
respiratory symptoms
• His nasal discharge has become thicker and more purulent
over the past week
• He also reports a low grade fever and facial pain but no other
HEENT symptoms
OUR PATIENT
• Past Medical History: Environmental allergies, recurrent
sinusitis (some episodes of which have been treated with
antibiotics), benign prostatic hyperplasia, melanoma (s/p
interferon treatment), and basal cell carcinoma
• Family Medical History: Noncontributory
• Medications: Fexofenadine, fluticasone nasal spray, ASA
• Allergies: Ampicillin (rash)
• He is married and works as a nurse educator at a local clinic
• He drinks alcohol infrequently and does not smoke cigarettes
OUR PATIENT
• Physical Examination: Noteworthy for T=99.6 deg. F, R > L
maxillary sinus tenderness, no discharge from nose, normal
TMs, and a mildly erythematous pharynx
• The patient requests antibiotics for his persistent sinus
symptoms
Would you treat Mr. X with antibiotics?
Text “Yes” or “No” to 22333
(It is not case sensitive)
CONTEXT
• Acute upper respiratory tract infections are common in
primary care practice
• While symptomatic management is indicated in the vast
majority of cases, patients often request antibiotic therapy
based upon the belief that it will have beneficial effects
• Antibiotics are prescribed at more than 100 million adult
ambulatory visits each year with 41% of these for respiratory
conditions
*Shapiro DJ, Hicks LA, Pavia AT, Hersh AL. Antibiotic prescribing for adults in
ambulatory care in the USA, 2007- 09. J Antimicrob Chemother. 2014;69:234-240.
CONTEXT
• Over 4.3 million adults are diagnosed with sinusitis each year,
and the majority of visits result in an antibiotic prescription,
most commonly a macrolide
• Concerns raised about the inappropriate use of antibiotics
include unanticipated side effects and toxicities, development
of multidrug resistance, and unnecessary cost to the patient
and society
*Fairlie T, Shapiro DJ, Hersh AL, Hicks LA. National trends in visit rates and antibiotic
prescribing for adults with acute sinusitis. Arch Intern Med. 2012;172:1513-1514.
CONTEXT
• Acute sinusitis presents with nasal congestion, purulent nasal
discharge, maxillary touch pain, facial pain or pressure, fever,
fatigue, cough, hyposmia or anosmia, ear pressure or fullness,
headache, and/or halitosis
• Symptom duration ranges from 1-33 days, but most cases
resolve within one week
• Most episodes are caused by viruses or allergens, and only a
small percentage is thought to be related to bacterial infection
*Meltzer EO, Schatz M, Nathan R, Garris C, Stanford RH, Kosinski M. Reliability, validity, and
responsiveness of the Rhinitis Control Assessment Test in patients with rhinitis. J Allergy
Clin Immunol. 2013;131:379-386.
CONTEXT
• The American College of Physicians and the Centers for
Disease Control and Prevention recently published advice for
high-value care on the appropriate use of antibiotics for acute
respiratory tract infections
• They conducted a literature review for evidence of the
effectiveness of antibiotic use in this setting
• It consisted of recent clinical guidelines from professional
societies supplemented by randomized controlled trials, metaanalyses, and systematic reviews
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians
and for the Centers for Disease Control and Prevention. Appropriate Antibiotic Use for Acute
Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of
Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016;164:425-434.
THE GUIDELINE
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for the Centers for Disease Control and Prevention. Appropriate
Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control
and Prevention. Ann Intern Med. 2016;164:425-434.
THE GUIDELINE
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians
and for the Centers for Disease Control and Prevention. Appropriate Antibiotic Use for Acute
Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of
Physicians and the Centers for Disease Control and Prevention. Ann Intern Med. 2016;164:425-434.
OTHER GUIDELINES
• AAO-HNS: Condition persists for >10 days without improvement
or worsening within 10 days after initial improvement
• Canadian: Condition persists for >7 days without improvement,
worsening after 5-7 days, or severe symptoms for 3-4 days
• European: Condition persists for >10 days, worsening after 5
days, or three or more severe symptoms
• IDSA: Condition persists for >10 days without improvement,
worsening after 5-6 days after initial improvement, or severe
symptoms for 3-4 days at beginning of illness
*Rosenfeld RM. Response to "Clinically Significant Rhinosinusitis Can Be Asymptomatic".
Otolaryngol Head Neck Surg. 2015;153:1078.
*Desrosiers M, Evans GA, Keith PK, Wright ED, Kaplan A, Bouchard J, et al. Canadian clinical
practice guidelines for acute and chronic rhinosinusitis. Allergy Asthma Clin Immunol. 2011;7:2.
*Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. EPOS 2012: European position paper on
rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012;50:1-12.
*Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, et al. IDSA clinical practice
guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e72-e112.
QUESTIONS TO DISCUSSANTS
To structure a debate between our two discussants, we mutually
agreed on the following key questions to consider when applying
these guidelines to clinical practice and to Mr. X in particular:
1) What clinical features support the diagnosis of acute sinusitis,
and how can a practitioner distinguish between allergy-related
symptoms, viral infection, and bacterial infection?
2) What are the risks and benefits of using antibiotic therapy to
treat acute sinusitis?
3) What would you recommend for Mr. X and why?
OUR MODERATOR & DISCUSSANTS
Deborah Cotton, MD, MPH (Moderator)
Professor of Medicine, Boston University School of Medicine
Deputy Editor, Annals of Internal Medicine
Diane Brockmeyer, MD
Division of General Medicine and Primary Care, BIDMC
Assistant Professor of Medicine, Harvard Medical School
Howard Gold, MD
Division of Infectious Diseases, BIDMC
Assistant Professor of Medicine, Harvard Medical School
Dr. Brockmeyer
An Argument for Antibiotic Use
*Reproduced with permission from Patel ZM, Hwang PH. Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment. In:
UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on September 9, 2016.) Copyright © 2016 UpToDate, Inc. For more
information visit www.uptodate.com.
What clinical features support the diagnosis of acute sinusitis?
How can a primary care practitioner distinguish between allergy-related
symptoms, viral infection, and bacterial infection?
Allergic
Viral
Bacterial
facial pressure
frontal headaches
anosmia
nasal congestion
postnasal drip
facial pressure
frontal headaches
anosmia
nasal congestion
postnasal drip
facial pressure
frontal headaches
anosmia
nasal congestion
postnasal drip
bilateral
rhinorrhea (watery, clear)
bilateral
mucous clear or purulent
typically improving or resolved
by day 7-10
sometimes fever
unilateral
mucous purulent
often chronic
no fever
sneezing
itching
eye symptoms
*Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice
guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1-S39.
*Ng ML, Warlow RS, Chrishanthan N, Ellis C, Walls R. Preliminary criteria for the definition of allergic rhinitis: a
systematic evaluation of clinical parameters in a disease cohort (I). Clin Exp Allergy. 2000;30:1314-1331.
*Gwaltney JM, Hendley JO, Simon G, Jordan WS. Rhinovirus infections in an industrial population. II.
Characteristics of illness and antibody response.. JAMA. 1967;202:494-500.
often lasts more than 10 days
often fever
maxillary toothache
cacosmia (sense of bad odor in the nose)
malaise
double worsening
unilateral facial tenderness on exam
elevated ESR and CRP
*Hickner JM, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA, et al. Principles of
appropriate antibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med.
2001;134:498-505.
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a general practice
population. BMJ. 1995;311:233-236.
Principles of Appropriate Antibiotic Use for Acute Sinusitis in Adults
*Hickner JM, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA, et al. Principles of
appropriate antibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med.
2001;134:498-505.
How are these predictors of bacterial
sinusitis derived?
• Description of one such study:
– 174 patients presented to primary care with
symptoms consistent with bacterial sinusitis
– All underwent CT scanning
– 122 (70%) had fluid in maxillary sinuses and
underwent sinus aspiration
– 92 (53% of total, 75% of those with fluid) had
mucopurulent fluid on the aspiration
– Cultures were then sent
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a
general practice population. BMJ. 1995;311:233-236.
Predicting acute maxillary sinusitis in a
general practice population
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a
general practice population. BMJ. 1995;311:233-236.
Predicting acute maxillary sinusitis in a
general practice population
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a
general practice population. BMJ. 1995;311:233-236.
Predicting acute maxillary sinusitis in a
general practice population
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a
general practice population. BMJ. 1995;311:233-236.
Features correlated with bacterial sinusitis
SINUSITIS NO SINUSITIS
OR (95% CI)
(n = 92)
(n = 82)
Unilateral Maxillary Pain
47 (51%)
31 (38%)
1.9 (1.0-3.4)
Maxillary toothache
61 (66%)
42 (51%)
1.9 (1.0-3.5)
Unilateral Maxillary
Tenderness on Exam
45 (49%)
28 (32%)
2.5 (1.2-5.2)
• ESR>10 mm/h in men, ESR>20 mm/h in women
• CRP>10 mg/l
*Reproduced from BMJ, Hansen JG, Schmidt H, Rosborg J, Lund E, Vol. 311,
pp233-236, © 1995 with permission from BMJ Publishing Group Ltd.
What clinical features support the diagnosis of acute sinusitis?
How can a primary care practitioner distinguish between allergy-related
symptoms, viral infection, and bacterial infection?
Allergic
Viral
Bacterial
facial pressure
frontal headaches
anosmia
nasal congestion
postnasal drip
facial pressure
frontal headaches
anosmia
nasal congestion
postnasal drip
facial pressure
frontal headaches
anosmia
nasal congestion
postnasal drip
bilateral
rhinorrhea (watery, clear)
bilateral
mucous clear or purulent
typically improving or resolved
by day 7-10
sometimes fever
unilateral
mucous purulent
often chronic
no fever
sneezing
itching
eye symptoms
*Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice
guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1-S39.
*Ng ML, Warlow RS, Chrishanthan N, Ellis C, Walls R. Preliminary criteria for the definition of allergic rhinitis: a
systematic evaluation of clinical parameters in a disease cohort (I). Clin Exp Allergy. 2000;30:1314-1331.
*Gwaltney JM, Hendley JO, Simon G, Jordan WS. Rhinovirus infections in an industrial population. II.
Characteristics of illness and antibody response.. JAMA. 1967;202:494-500.
often lasts more than 10 days
often fever
maxillary toothache
cacosmia (sense of bad odor in the nose)
malaise
double worsening
unilateral facial tenderness on exam
elevated ESR and CRP
*Hickner JM, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA, et al. Principles of
appropriate antibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med.
2001;134:498-505.
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a general practice
population. BMJ. 1995;311:233-236.
Other diagnoses
*Reproduced with permission from Patel ZM, Hwang PH. Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment. In:
UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on September 9, 2016.) Copyright © 2016 UpToDate, Inc. For more
information visit www.uptodate.com.
What are the risks of using antibiotic therapy
to treat acute sinusitis?
• Mild patient-specific risks:
– Self-limited diarrhea
– Other GI side effects
– Vaginal or other yeast infection
– Cost
– Medication interactions
– Personal risk for subsequent resistance
What are the risks of using antibiotic therapy
to treat acute sinusitis?
• Moderate patient-specific risks:
– Allergic reactions
– C. difficile infection
– Tendinopathy, neuropathy (fluroquinolones)
• Severe patient-specific risks:
– Anaphylaxis
– Stevens-Johnson Syndrome
– Severe C. difficile infection
Drug Safety Communication, July 2016
FDA advises restricting fluoroquinolone
antibiotic use for certain uncomplicated
infections; warns about disabling side
effects that can occur together
*FDA Drug Safety Communication: FDA updates warnings for oral and injectable
fluoroquinolone antibiotics due to disabling side effects: US FDA; 2016. Available from:
http://www.fda.gov/Drugs/DrugSafety/ucm511530.htm.
What are the risks of using antibiotic therapy
to treat acute sinusitis?
• Community and Societal Risks:
– Cost
– Increasingly resistant organisms, including
multidrug resistance
*Rauber JM, Carneiro M, Arnhold GH3, Zanotto MB, Wappler PR, Baggiotto B et al. Multidrug-resistant
Staphylococcus spp and its impact on patient outcome. Am J Infect Control. 2016;44:e261-e263.
*Wener KM, Schechner V, Gold HS, Wright SB, Carmeli Y, et al. Treatment with fluoroquinolones or with
beta-lactam-beta-lactamase inhibitor combinations is a risk factor for isolation of extended-spectrumbeta-lactamase-producing Klebsiella species in hospitalized patients. Antimicrob Agents Chemother.
2010;54:2010-2016.
What are the benefits of using antibiotic therapy
to treat acute sinusitis?
• Postulated benefits of treating bacterial infection
(although lack of evidence for many):
– Shortened duration of symptoms
– Fewer lost work days
– Fewer medical visits
– Decreased risk of (rare) serious complications, such
as orbital cellulitis, meningitis, or abscess
– There is some evidence that treatment can be costeffective if diagnostic criteria are carefully applied
*Balk EM, Zucker DR, Engels EA, Wong JB, Williams JW Jr, Lau J. Strategies for diagnosing and treating suspected
acute bacterial sinusitis: a cost-effectiveness analysis. J Gen Intern Med. 2001;16:701-711.
*Anzai Y, Jarvik JG, Sullivan SD, Hollingworth W. The cost-effectiveness of the management of acute sinusitis.
Am J Rhinol. 2007;21:444-451.
Cochrane Review 2012:
Benefit of antibiotics is likely small and should be
reserved for selected cases
*Lemiengre, van Driel ML, Merenstein D, Young J, De Sutter AI. Antibiotics for clinically
diagnosed acute rhinosinusitis in adults. Cochrane Database Syst Rev. 2012;10:CD006089.
Cochrane Review 2012:
Many patients had simple URIs
• “The three most used inclusion criteria were
nasal discharge, facial pain, and common cold
or upper respiratory tract infection”
• “The mean duration of symptoms before
inclusion was approximately seven days”
*Lemiengre, van Driel ML, Merenstein D, Young J, De Sutter AI. Antibiotics for clinically
diagnosed acute rhinosinusitis in adults. Cochrane Database Syst Rev. 2012;10:CD006089.
Trial of 5 days moxifloxacin vs. placebo
• Cure rates higher in moxifloxicin (78% vs 67%) but
not statistically significant (p=0.19)
• But…patients chose to leave the study due to lack of
benefit at much higher rates in placebo group (8%
moxifloxicin, 22% placebo) (p=0.03)
*Hadley JA, Mösges R, Desrosiers M, Haverstock D, van Veenhuyzen D, Herman-Gnjidic Z.
Moxifloxacin five-day therapy versus placebo in acute bacterial rhinosinusitis. Laryngoscope.
2010;120:1057-1062.
Trial of 5 days moxifloxacin vs. placebo
• Moxifloxacin had secondary efficacy:
– Decreased SNOT-16 score
– Improvement in activity impairment scores
– Lower requirement for symptomatic measures
– Adverse events similar in both groups
*Hadley JA, Mösges R, Desrosiers M, Haverstock D, van Veenhuyzen D, Herman-Gnjidic Z.
Moxifloxacin five-day therapy versus placebo in acute bacterial rhinosinusitis. Laryngoscope.
2010;120:1057-1062.
What would you recommend to Mr. X and why?
• Shared decision-making
• Doxycycline 100 mg orally twice a day for 7 days
• Symptomatic care
Is it plausible that this is bacterial sinusitis?
Allergic
Viral
Bacterial
facial pressure
facial pressure
facial pressure
frontal headaches
frontal headaches
frontal headaches
anosmia
anosmia
anosmia
nasal congestion
nasal congestion
nasal congestion
postnasal drip
postnasal drip
postnasal drip
bilateral
bilateral
unilateral
rhinorrhea (watery, clear)
mucous clear or purulent
mucous purulent
often chronic
typically improves by day 10
often lasts more than 10 days
no fever
sometimes fever
often fever
sneezing
maxillary toothache
itching
cacosmia (sense of bad odor in the nose)
eye symptoms
malaise
double worsening
unilateral facial tenderness on exam
elevated ESR and CRP
*Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice
guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1-S39.
*Ng ML, Warlow RS, Chrishanthan N, Ellis C, Walls R. Preliminary criteria for the definition of allergic rhinitis: a
systematic evaluation of clinical parameters in a disease cohort (I). Clin Exp Allergy. 2000;30:1314-1331.
*Gwaltney JM, Hendley JO, Simon G, Jordan WS. Rhinovirus infections in an industrial population. II.
Characteristics of illness and antibody response.. JAMA. 1967;202:494-500.
*Hickner JM, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA, et al. Principles of
appropriate antibiotic use for acute rhinosinusitis in adults: background. Ann Intern Med.
2001;134:498-505.
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a general practice
population. BMJ. 1995;311:233-236.
THE GUIDELINE
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of
Physicians and for the Centers for Disease Control and Prevention. Appropriate
Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care
From the American College of Physicians and the Centers for Disease Control and
Prevention. Ann Intern Med. 2016;164:425-434.
Predicting acute maxillary sinusitis in a
general practice population
*Hansen JG, Schmidt H, Rosborg J, Lund E. Predicting acute maxillary sinusitis in a
general practice population. BMJ. 1995;311:233-236.
Antibiotic Therapy – For Mr. X, doxycycline 100 mg
orally twice a day for 7 days
Guideline:
First line antibiotic:
If Penicillin allergy:
ACP Guideline 2016
amoxicilin with clavulanate doxycycline
amoxicillin
levofloxacin
moxifloxacin
Otolaryngology 2015
high dose amoxicillin
doxycycline
amoxicilin with clavulanate levofloxacin
moxifloxacin
clindamycin plus cefixime or cefpodoxime
ISDA Guidelines 2012
amoxicilin with clavulanate doxycycline
levofloxacin
moxifloxacin
FDA Drug Safety Communication, 7/26/2016
*Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, et
al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in
children and adults. Clin Infect Dis. 2012;54:e72-e112.
Avoid fluroquinolones unless no other
treatment options, due to potential for
disabling and potentially permanent side
effects, including tendonopathy, nerve,
and CNS side effects
*Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K,
Kramper M, et al. Clinical practice guideline (update): adult sinusitis.
Otolaryngol Head Neck Surg. 2015;152:S1-S39.
Algorithm for the management of acute bacterial rhinosinusitis
*Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA,
et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis
in children and adults. Clin Infect Dis. 2012;54:e72-e112.
Benefits of shared decision-making
• Improved patient satisfaction
• Improved patient medical knowledge
• Decreased sense of conflict
*Joosten EA, DeFuentes-Merillas L, de Weert GH, Sensky T, van der Staak CP, de Jong CA. Systematic
review of the effects of shared decision-making on patient satisfaction, treatment adherence and
health status. Psychother Psychosom. 2008;77:219-222.
*Altin SV, Stock S. The impact of health literacy, patient-centered communication and shared decisionmaking on patients' satisfaction with care received in German primary care practices. BMC Health Serv
Res. 2016;16:450.
Symptomatic Management
•
•
•
•
•
Oral analgesics
Saline nasal irrigation
Decongestants (oral or topical)
Intranasal steroids
Chicken soup AKA: natural L-carnosine peptide
("bioactivated Jewish penicillin")
*Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K,
Kramper M, et al. Clinical practice guideline (update): adult sinusitis.
Otolaryngol Head Neck Surg. 2015;152:S1-S39.
*Saketkhoo K, Januszkiewicz A, Sackner MA. Effects of drinking hot
water, cold water, and chicken soup on nasal mucus velocity and nasal
airflow resistance. Chest. 1978;74:408-410.
*Renard BO, Ertl RF, Gossman GL, Robbins RA, Rennard SI. Chicken soup
inhibits neutrophil chemotaxis in vitro. Chest. 2000;118:1150-1157.
*Babizhayey MA, Deyev AI, Yegorov YE. Non-hydrolyzed in digestive tract and blood
natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of
tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO)
production, cytostasis, and NO-dependent inhibition of influenza virus replication in
macrophages in the human body infected with the virulent swine influenza A (H1N1)
virus. J Basic Clin Physiol Pharmacol. 2013;24:1-26.
Dr. Gold
An Argument against Antibiotic Use
Overview
• Most cases of acute sinusitis are caused by viruses or allergens and
resolve within one week
• <2% of acute viral URI cases are complicated by bacterial
infection
• Acute sinusitis can generally be managed symptomatically
• Meta-analysis of adults with clinically diagnosed acute sinusitis
– Number needed to treat with antibiotics was 18 for 1 patient
to be cured more rapidly than with placebo
– For every 8 patients treated, one will be harmed by adverse
effects of antibiotics
*Lemiengre, van Driel ML, Merenstein D, Young J, De Sutter AI. Antibiotics for clinically
diagnosed acute rhinosinusitis in adults. Cochrane Database Syst Rev. 2012;10:CD006089.
THE GUIDELINE
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of
Physicians and for the Centers for Disease Control and Prevention. Appropriate
Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care
From the American College of Physicians and the Centers for Disease Control and
Prevention. Ann Intern Med. 2016;164:425-434.
Symptoms of acute sinusitis
• Acute sinusitis presents with
–
–
–
–
–
–
nasal congestion
maxillary touch pain
fever
cough
ear pressure or fullness
halitosis
–
–
–
–
–
purulent nasal discharge
facial pain or pressure
fatigue
hyposmia or anosmia
headache
• Clinicians should reserve antibiotic treatment for acute
sinusitis for patients with persistent symptoms for
more than 10 days
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of
Physicians and for the Centers for Disease Control and Prevention. Appropriate
Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care
From the American College of Physicians and the Centers for Disease Control and
Prevention. Ann Intern Med. 2016;164:425-434.
Mr. X appears to meet criteria
• Acute sinusitis presents with
–
–
–
–
–
–
nasal congestion 
maxillary touch pain 
fever 
cough
ear pressure or fullness
halitosis
–
–
–
–
–
purulent nasal discharge 
facial pain or pressure 
fatigue 
hyposmia or anosmia
headache
• Clinicians should reserve antibiotic treatment for acute
rhinosinusitis for patients with persistent symptoms
for more than 10 days 
General thoughts about guidelines
• Guidelines are not an excuse to turn off your brain
• Regard the limitations in the data noted by guideline
authors, the caveats, the nuances
• Question authority – scratch the surface of a guideline,
and you will often find that there is often room for
disagreement
Psychology matters
• Antibiotics are great, but not magic
• Association  Causation
• Antibiotics are terrible, and poor anxiolytics
Question 1
What clinical features support the diagnosis of
acute sinusitis, and how can a primary care
practitioner distinguish between allergy-related
symptoms, viral infection, and bacterial
infection?
Symptoms and signs in culture-proven acute maxillary
sinusitis in a general practice population
•
•
•
•
•
ABRS
(n = 45)
No ABRS
(n = 82)
OR (95% CI)
T > 38°C (100.4°F)
16 (35.5%)
9 (11.0%)
4.6 (1.9-11.2)
Maxillary toothache
33 (73.3%)
42 (51.2%)
2.9 (1.3-6.3)
Self-reported h/o
sinusitis
28 (62.2%)
66 (80.5%)
0.4 (0.2-0.9)
CRP 11-49 (mg/L)
17 (37.8%)
10 (12.2%)
8.9 (4-22)
CRP >49 (mg/L)
16 (35.6%)
8 (9.8%)
10.5 (4-27)
Preceding URTI
Cough
Nasal congestion
Pain bending forward
Anosmia
•
•
•
Cacosmia
• Tenderness on tapping over
Purulent nasal discharge maxillary sinus
Purulent pharyngeal
discharge
*Adapted from Symptoms and signs in culture-proven acute maxillary sinusitis
in a general practice population, Hansen JG, Højbjerg T, Rosborg J. Copyright ©
2009 APMIS. Reproduced with permission of Blackwell Publishing Ltd.
Are any clinical findings helpful?
No Evidence for Distinguishing Bacterial from Viral Acute Rhinosinusitis Using
Symptom Duration and Purulent Rhinorrhea: A Systematic Review of the
Evidence Base
• “…distinguish…based on purulent rhinorrhea…not supported by evidence”
• “after 10 days, antibiotic therapy may seem a reasonable empirical option”
No Evidence for Distinguishing Bacterial from Viral Acute Rhinosinusitis Using
Fever and Facial/Dental Pain: A Systematic Review of the Evidence Base
• “…should not be used …to distinguish between a bacterial and viral source of
acute rhinosinusitis”
*van den Broek MF, Gudden C, Kluijfhout WP, Stam-Slob MC, Aarts MC, Kaper NM, et al. No
evidence for distinguishing bacterial from viral acute rhinosinusitis using symptom
duration and purulent rhinorrhea: a systematic review of the evidence base. Otolaryngol
Head Neck Surg. 2014;150:533-537.
*Hauer AJ, Luiten EL, van Erp NF, Blase PE, Aarts MC, Kaper NM, et al. No evidence for
distinguishing bacterial from viral acute rhinosinusitis using fever and facial/dental pain: a
systematic review of the evidence base. Otolaryngol Head Neck Surg. 2014;150:28-33.
Question 1 Answer
• No individual symptom or group of symptoms is highly
sensitive or specific for the diagnosis of acute bacterial
sinusitis
• Radiography (x-ray/CT scan) is not useful in determining
the cause of acute sinusitis
• Difficult to determine the etiology of acute sinusitis, so
the practitioner and the patient have to accept diagnostic
uncertainty
Question 2
What are the risks and benefits of using
antibiotic therapy to treat acute sinusitis?
Emergency department visits for antibioticassociated adverse events
• Estimated 142,505 visits/yr (95% CI, 116,506–168,504) to
US EDs for drug-related adverse events attributable to
systemic antibiotics
• Antibiotics implicated in 19.3% of ED visits for drugrelated adverse events
• Most for allergic reactions (78.7% of visits)
• Estimated annual ED visits/10,000 outpatient
prescriptions ranged from 5.1 (macrolides) to 13
(penicillins) to >20 (moxifloxacin)
*Shehab N, Patel PR, Srinivasan A, Budnitz DS. Emergency
department visits for antibiotic-associated adverse events. Clin
Infect Dis. 2008;47:735-743.
Safety concerns with commonly prescribed
antibiotics for URIs - Macrolides
• Azithromycin: Drug Safety Communication - Risk of Potentially Fatal
Heart Rhythms (3/12/2013)
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm343350.htm
Safety concerns with commonly prescribed
antibiotics for URIs - Fluoroquinolones
• FDA Updates Warnings for Fluoroquinolones - Drug Information
Update (7/26/2016)
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513183.htm?source=govdelivery&utm_mediu
m=email&utm_source=govdelivery
Significant decline in erythromycin resistance among group A
streptococci with reduced macrolide use
*From New England Journal of Medicine, Seppälä H, Klaukka T, VuopioVarkila J, Muotiala A, Helenius H, Lager K, Huovinen P, The effect of
changes in the consumption of macrolide antibiotics on erythromycin
resistance in group A streptococci in Finland. Finnish Study Group for
Antimicrobial Resistance, Vol 337, pp441, Copyright © 1997
Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
Question 2 Answer
• Only risks and no benefits of using antibiotic therapy to
treat viral sinusitis
– Allergies/ADR
– Drug resistance
– Overgrowth syndromes
– Drug-drug interactions
• Benefits of antibiotics to treat bacterial sinusitis
– Severe disease: benefits > risks
– Mild disease: benefits < risks
Question 3
What would you recommend for Mr. X and why?
Conclusion #3 of ACP and CDC recommendations
for appropriate use of antibiotics for acute RTI
• Clinicians should reserve antibiotic treatment for
acute rhinosinusitis for patients with…
• “Antibiotics may be prescribed…”
• “Limited benefit”
• NNT= 18 > NNH = 8
*Harris AM, Hicks LA, Qaseem A; High Value Care Task Force of the American College of Physicians and for
the Centers for Disease Control and Prevention. Appropriate Antibiotic Use for Acute Respiratory Tract
Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for
Disease Control and Prevention. Ann Intern Med. 2016;164:425-434.
*Lemiengre MB, van Driel ML, Merenstein D, Young J, De Sutter AI. Antibiotics for clinically diagnosed acute
rhinosinusitis in adults. Cochrane Database Syst Rev. 2012;10:CD006089.
Moxifloxacin five‐day therapy versus placebo in
acute bacterial rhinosinusitis
• Prospective, multicenter, randomized, double-blind,
phase III trial
• Enrolled 375 patients with clinical and radiographic
evidence of acute sinusitis
• 118/374 (31.6%) microbiologically confirmed by sinus
puncture
• Clinical success rates were not significantly higher for
moxifloxacin (78.1%, 57/73) vs. placebo (66.7%, 30/45)
(P=0.189) in mITT subjects
*Hadley JA, Mösges R, Desrosiers M, Haverstock D, van Veenhuyzen D, Herman-Gnjidic Z. Moxifloxacin
five-day therapy versus placebo in acute bacterial rhinosinusitis. Laryngoscope. 2010;120:1057-1062.
Safety of reduced antibiotic prescribing for self-limiting
respiratory tract infections in primary care: cohort study using
electronic health records
*Gulliford MC, Moore MV, Little P, Hay AD, Fox R, Prevost AT, et al.
Safety of reduced antibiotic prescribing for self limiting respiratory tract
infections in primary care: cohort study using electronic health records.
BMJ. 2016;354:i3410.
Question 3 Answer
• I would not recommend antibiotics at this time
• I would recommend documentation of fever and maximizing
symptomatic treatment
• Reassure Mr. X he will probably improve without antibiotics, but
would provide them depending on his clinical course
• Fever, worsening facial pain or swelling, or lack of improvement
with maximal symptomatic treatment  reconsider antibiotics
• I would not recommend sinus imaging with x-ray or CT scan,
otorhinolaryngology referral, or sinus cultures by puncture or
endoscopic sampling of the middle meatus
Question 3 Answer
• Were Mr. X to develop more compelling symptoms or signs of
acute bacterial sinusitis, I would recommend treatment:
– If he has tolerated other penicillins 
amoxicillin/clavulanate 875 mg PO twice daily for 5-7 days
– If he has not tolerated other penicillins  doxycycline 100
mg twice daily for 5-7 days
– Generally would not recommend quinolones or macrolides
in this setting
*Chow AW, Benninger MS, Brook I, Brozek JL, Goldstein EJ, Hicks LA, et al. IDSA clinical practice
guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e72e112.
Dr. Brockmeyer & Dr. Gold
A Discussion
Would you treat Mr. X with antibiotics?
Text “Yes” or “No” to 22333
(It is not case sensitive)
*If you have not yet joined the voting session, text
“BIDMC” to 22333, then follow the directions above.
We would like to thank…
Our Patient, Mr. X
Diane Brockmeyer, MD & Howard Gold, MD
Risa Burns, MD, MPH
Deborah Cotton, MD, MPH
Howard Libman, MD
Eileen Reynolds, MD
Gerald Smetana, MD
Last Minute Productions
BIDMC Media Services
Kendra McKinnon
© 2016 American College of Physicians
The information contained herein should never be
used as a substitute for clinical judgment.