supplement to

Available at www.jfponline.com February 2008

Managing
respiratory tract
infections
in patients with
variables associated with
treatment failure

This material was submitted by PharmaWrite® and supported by PRICARA®, Division of Ortho-McNeil-Janssen
Pharmaceuticals, Inc. It was edited and peer reviewed by The Journal of Family Practice.
Managing respiratory tract infections
in patients with variables associated
with treatment failure
Is it bacterial or viral?
Criteria for distinguishing bacterial
and viral infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S5
Michael Benninger, MD
Chairman, Head and Neck Institute
The Cleveland Clinic
Cleveland, Ohio
John Segreti, MD
Rush Medical College
Rush University Medical Center
Chicago, Illinois

Patient variables associated

with treatment failure in respiratory
tract infections.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S12
Hans H. Liu, MD
Professor of Medicine
Jefferson Medical College
Philadelphia, Pennsylvania
Infectious Diseases Consultant
Bryn Mawr Medical Specialists Association
Bryn Mawr, Pennsylvania
Robert E. Siegel, MD
James J. Peters Veterans Affairs Medical Center
New York, New York

Treatment recommendations for

patients with common respiratory tract
infections with variables indicative of
treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . S19
Raymond S. Basri, MD
Clinical Assistant Professor of Medicine
New York Medical College
Valhalla, New York
David A. Weiland, MD
Medical Director
The Hospice of the South Florida Suncoast
Pinellas Park, Florida
Greg L. Ledgerwood, MD
General Practitioner and Asthma Certified Educator (AE-C)
Brewster Medical Center
Brewster, Washington

S Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice Copyright © 2008 Dowden Health Media
Introduction by Hans H. Liu, MD
T
his publication reviews the challenges
faced by clinicians in the diagnosis and
management of bacterial respiratory tract
infection (RTI). It highlights patient factors that
may be indicative of treatment failure and pro-
vides recommendations to help clinicians most
effectively manage their patients with RTIs.
The articles are based on the proceedings of a
May 2006 meeting of a multispecialty working
group held in Chicago. Participants included
infectious disease specialists, pulmonologists,
otolaryngologists, and primary care physicians.
The articles in this supplement reflect the par-
ticipants’ own conclusions and are based on
their collective clinical experience and on cur-
rently available treatment guidelines.
The participants noted that a major chal-
lenge for clinicians is the sheer number of pa-
tient visits from September through March,
often called “the respiratory season.” Infectious
diseases are among the most common reasons
patients consult their health care professionals,
accounting for more than one fifth (21.2%) of
all nonroutine visits and approximately 129 mil-
lion visits annually. 1 Between 1980 and 1990,
these visits increased steadily (2.14% annually
[P = .006]), 1 with significant growth in the num-
ber of upper respiratory tract infections (URTIs)
(P = .02), lower respiratory tract infections (LRTIs),
and influenza (P = .008). 1 Coupled with this in-
creased volume of patient visits for infectious
diseases, and RTIs specifically, are conflicting
pressures such as limited time for evaluating pa-
tients, managed-care efficiency requirements,
and complicated patient issues resulting from
Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008
an aging and sicker population.
During the course of the group’s discus-
sion, the participants identified 3 areas that are
critical for improvement of patient outcomes in
the primary care setting:
1 Reducing
n resistance to antibiotics by ad-
herence to appropriate prescribing of these
agents. 2-4 As will be discussed in “Is it bacterial
or viral? Criteria for distinguishing bacterial and
viral infections” (see page S5), the first challenge
for clinicians is to determine more accurately
whether the origin of an RTI is viral or bacterial.
Antibacterials, although ineffective against viral
infections, are often prescribed.5 National, re-
gional, and local resistance patterns must also
be carefully considered, as will be discussed
in “Treatment recommendations for patients
with common respiratory tract infections with
variables indicative of treatment failure” (see
page S19).
2 Identifying
n those patients with RTIs with
patient variables that may be indicative of
treatment failure and recognizing the con-
sequences of treatment failure for such pa-
tients. Which patients are at increased risk? Do
they have underlying comorbid conditions or
social complications? Are they harboring resis-
tant pathogens? Which patients need a more
aggressive therapeutic approach? The chal-
lenges of providing care for at-risk populations
are discussed in “Patient variables associated
with treatment failure in respiratory tract infec-
tions” (see page S12).
Continued
S
Introduction by Hans H. Liu, MD, FACP

3 Interpreting and synthesizing treatment rec-

n of treatment failure” (see page S19) provides a
ommendations developed by specialty medical
societies for primary care practitioners. Spe-
cialty medical societies have developed treatment
guidelines to help guide clinicians in the care of
patients with specific RTIs, including acute bacte-
rial rhinosinusitis, acute exacerbation of chronic
bronchitis, and community-acquired pneumonia.6-9
However, these guidelines are usually oriented
toward the needs of specialists and are typically
written using their specialized terms. “Treatment
recommendations for patients with common re-
spiratory tract infections with variables indicative
user-friendly interpretation and synthesis of avail-
able guidelines that can be implemented in the
busy primary care setting.
We hope that this publication will be of value to
busy clinicians and will help you identify patients
whose health profile and personal circumstances
require careful consideration in formulating ap-
propriate treatment regimens for RTIs.
The authors thank PRICARA®, Division of
Ortho-McNeil-Janssen Pharmaceuticals, Inc, for
providing the resources to hold the meeting and
for funding the costs of this supplement.

References

1. Armstrong GL, Pinner RW. Outpatient visits
for infectious diseases in the United States, 1980
through 1996. Arch Intern Med. 1999;159:2531-
2536.
2. Slama TG, Amin A, Brunton SA, et al, for the
Council for Appropriate and Rational Antibiotic
Therapy. A clinician’s guide to the appropriate
and accurate use of antibiotics: the Council for
Appropriate and Rational Antibiotic Therapy
(CARAT) criteria. Am J Med. 2005;118(suppl
7A):1S-6S.
3. Low DE. Antimicrobial drug use and re-
sistance among respiratory pathogens in the
community. Clin Infect Dis. 2001;33(suppl 3):
S206-S213.
4. File TM Jr. Overview of resistance in the
1990s. Chest. 1999;115(suppl):3S-8S.
5. Gonzales R, Malone DC, Maselli JH, et al.
Excessive antibiotic use for acute respiratory
infections in the United States. Clin Infect Dis.
2001;33:757-762.
6. Niederman MS, Mandell LA, Anzueto A, et al,
for the ad-hoc subcommittee of the Assembly on
Microbiology, Tuberculosis, and Pulmonary In-
fections, American Thoracic Society. Guidelines
for the management of adults with community-
acquired pneumonia: diagnosis, assessment of
severity, antimicrobial therapy, and prevention.
Am J Respir Crit Care Med. 2001;163:1730-
1754.
7. Mandell LA, Wunderink RG, Anzueto A,
et al. Infectious Diseases Society of America/
American Thoracic Society consensus guide-
lines on the management of community-
acquired pneumonia in adults. Clin Infect Dis.
2007;44(suppl 2):527-572.
8. Anon JB, Jacobs MR, Poole MD, et al, for
the Sinus and Allergy Health Partnership. Anti-
microbial treatment guidelines for acute bacte-
rial rhinosinusitis. Otolaryngol Head Neck Surg.
2004;130(suppl 1):1-45.
9. Balter MS, La Forge J, Low DE, et al, and the
Chronic Bronchitis Working Group on behalf of
the Canadian Thoracic Society and the Canadian
Infectious Disease Society. Canadian guidelines
for the management of acute exacerbations of
chronic bronchitis. Can Respir J. 2003;10(suppl
B):3B-32B.

S Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice

 Available at www.jfponline.com

Is it bacterial or viral?
Criteria for distinguishing bacterial
and viral infections
Michael Benninger, MD • John Segreti, MD

M
uch discussion in the medical literature has focused
on the consequences of inappropriate prescribing of
Key Points
antibiotics, including the increased potential for ad- o Differentiation of bacterial from viral
infections is essential for appropriate
verse events, higher treatment costs, and the development of
treatment. Additionally, unnecessary
bacterial resistance. What factors contribute to inappropriate use of antibacterial prescriptions
prescribing? This article reviews challenges facing clinicians can lead to increases in adverse
and suggests strategies to address these problems. reactions and treatment costs and
Managed health care systems place significant time con- promotion of resistant bacteria.
straints on primary care practitioners. Prescribing behavior o Inappropriate, excessive, and costly
may be affected in several ways. In the short time available for antibiotic prescribing is of concern:
key respiratory pathogens are
an office visit, it can be challenging to differentiate viral versus
becoming increasingly resistant to
bacterial infections in diseases that share similar clinical signs commonly used antibiotics such as
and symptoms. In such a setting, writing a prescription for penicillins and macrolides.
an antibiotic can be perceived as the quickest way to end the o Currently, the number of antibiotic
visit.1 Additionally, patients often pressure their clinicians to prescriptions far surpasses
prescribe an antibiotic, whether or not it is indicated, because the number of actual bacterial
of their impatience to feel well or because of psychological infections.
expectations associated with office visits.1 The issue of time o Acute rhinosinusitis, acute
(or lack of it) presents another challenge as clinicians struggle exacerbation of chronic bronchitis,
and community-acquired pneumonia
to keep abreast of local resistance trends so they can select
are 3 infectious diseases commonly
an appropriate antibiotic when a bacterial infection has been encountered by clinicians.
diagnosed.
o Most cases of rhinosinusitis are
Clinicians may find it easier to cope with these pressures viral in origin, whereas acute
if they can more confidently distinguish between bacterial and exacerbation of chronic bronchitis
viral infections. This article seeks to provide busy primary and community-acquired pneumonia
care practitioners with tools to quickly determine the etiology typically result from bacterial
infection.
of common respiratory tract infections (RTIs) such as acute

Disclosures: Dr Benninger has disclosed that he has received research support from Naryx Pharma, Inc., and Novartis Pharmaceuticals; has
served as a consultant to Abbott Laboratories, Ortho-McNeil-Janssen Pharmaceuticals, Inc, and sanofi-aventis; and has served on the speakers
bureau of Abbott Laboratories. Dr Segreti has disclosed that he has served as a consultant to Pfizer Inc, Ortho-McNeil-Janssen Pharmaceuti-
cals, Inc, and Wyeth Pharmaceuticals; has served on the speakers bureau of Elan, Ortho-McNeil-Janssen Pharmaceuticals, Inc, Pfizer Inc, and
Wyeth Pharmaceuticals; and is a stockholder of Pfizer Inc.

Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S

C ri t eria f o r di st ing ui shing bac te ria l a nd v ira l in fect ions

FIGURE
of this total, $726 million (55%) was
Primary care office visits and antibiotic prescriptions spent on inappropriate antibiotic pre-
for acute respiratory illnesses in the United States scriptions.3 Although the estimated
n Office visits bacterial prevalence of bronchitis
25 n Antibiotic prescription was 10%, antibiotics were prescribed
n Bacterial prevalence
Number of Visits (millions)

20
15
10
5
0
I essary treatment costs, inappropri-
UR ed
ia itis
M inus
itis s ar
Ot ino Ph
Rh
Data from the 1998 National Ambulatory Medical Care Survey (National
Center for Health Statistics).
URI, upper respiratory infection.
Modified with permission from Gonzales R, Malone DC, Maselli JH, Sande MA.
Excessive antibiotic use for acute respiratory infections in the United States. Clin Infect
Dis. 2001;33:757-762. © 2001 The University of Chicago Press.
rhinosinusitis, acute exacerbation of chronic
bronchitis (AECB), and community-acquired
pneumonia (CAP), thus enabling clinicians to
treat these diseases appropriately.
How common is inappropriate
antibiotic prescribing?
Although viral infections do not respond to anti-
biotics, prescriptions for these agents exceed the
number of actual bacterial infections. Results of
the National Ambulatory Medical Care Survey
(1991-1999) show that viral diseases such as vi-
ral rhinosinusitis, unspecified upper respiratory
tract infections (URTIs), and acute bronchitis
accounted for 22% of adult prescriptions for
broad-spectrum antibiotics.2 A comparison of
1998 data underscores the extent of the prob-
lem. A published study revealed that more than
half of the 22.6 million antibiotics prescribed
for acute RTIs, such as bronchitis and unspeci-
fied URTIs, were used for infections of probable
nonbacterial origin.3 The cost of treatment of
acute RTIs totaled approximately $1.32 billion;
for 59% of the 13 million patients
diagnosed with bronchitis (Fig ure ).3
Clearly, inappropriate prescribing of
antibiotics for acute RTIs has become
excessive and costly.4
In addition to incurring unnec-
itis itis
yng n ch ate antibiotic use has been shown
Br
o
to decrease the utility of antibiotics
because of resistance to commonly
prescribed agents.5-7 The use of anti-
biotics and certain vaccines poses
unique risks: they are the sole thera-
peutic classes that may affect not only
individual patients but also their fam-
ilies, coworkers, friends, and others with whom
they come in contact, by potentially infecting
them with resistant pathogens.1
Resistance to penicillin and macrolides is par-
ticularly high.1,8-10 Several studies have found that
rates of penicillin resistance among Streptococ-
cus pneumoniae range from 9.8% to 21.2%.9,10
Similarly, rates of macrolide (azithromycin and
erythromycin) resistance have been estimated at
17.3% to 40.4%.8,10 In addition, overuse of anti-
biotics is likely to exacerbate the resistance prob-
lem1; decreasing inappropriate use of antibiotics
should be considered a first step toward attempt-
ing to control resistance.1
Rhinosinusitis: Issues for clinicians
Epidemiology and burden of disease
Viruses are responsible for the traditional “com-
mon cold” and related acute viral RTIs. In 1997,
the annual incidence of viral RTIs among adults
in the United States was 2 to 3 illnesses per per-
son.11,12 In the 1990s, it was estimated that ap-
proximately 90% of cases had a confirmed viral

S Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice

 Table 1
component.12 In contrast, acute bacterial rhinosi-
nusitis (ABS) occurs in only 0.5% to 2% of these Pathogens commonly associated
cases11,12; however, given the large number of re- with bacterial RTIs
spiratory illnesses occurring annually (>1 billion ABS
as of 200412), that percentage translates to an Streptococcus pneumoniae
estimated 20 million cases. Haemophilus influenzae
The socioeconomic burden of URTIs, includ- Moraxella catarrhalis

ing sinusitis, is considerable, in part because of their Staphylococcus aureus

Anaerobes
high prevalence. In 1996, rhinosinusitis treatment
Streptococcus spp
costs totaled $3.39 billion.13 Work productivity
and quality of life also declined. A random survey ABECB

conducted by the University of Pittsburgh School Haemophilus influenzae

Streptococcus pneumoniae
of Medicine in 2004 evaluated 606 self-identified
Moraxella catarrhalis
recurrent chronic rhinosinusitis or bronchitis pa-
Staphylococcus aureus
tients. Of these respondents, 25% reported miss-
Pseudomonas aeruginosa
ing 3 or more workdays because of illness,14 and Opportunistic gram-negative bacteria
another 23% reported missing 1 to 2 workdays. In Mycoplasma pneumoniae
all, sinusitis may account for >30 million sick days
CAP
each year.14 In addition, 58% of the respondents
Typical pathogens
said they were likely to curtail leisure activities be- Streptococcus pneumoniae
cause of rhinosinusitis or bronchitis,14 suggesting Haemophilus influenzae
reduced quality of life for these patients.14 Moraxella catarrhalis
Limited data are available to assess the prev- Staphylococcus aureus
alence of viral etiology in acute rhinosinusitis be- Streptococcus pyogenes
cause few sinus aspirates are tested for viruses.11 Neisseria meningitides
However, one study of aspirates from adult pa- Klebsiella pneumoniae and other gram-negative rods
tients with rhinosinusitis identified the 3 most Atypical pathogens
common viral pathogens as rhinovirus, influenza Mycoplasma pneumoniae
virus, and parainfluenza virus.15 Chlamydia pneumoniae
Tabl e 1 lists the bacterial pathogens common- Legionella spp

ly associated with RTIs. In ABS, S pneumoniae is
the most common pathogen found (20%-43%
of cases), followed by Haemophilus influenzae
(22%-35%), and Moraxella catarrhalis (2%-
10%).12 A recent meta-analysis of prospective,
ABECB, acute bacterial exacerbation of chronic bronchitis;
ABS, acute bacterial rhinosinusitis; CAP, community-acquired
pneumonia; RTI, respiratory tract infection.
Anon JB, et al. Otolaryngol Head Neck Surg. 2004;130 (suppl 1):
1-45; Ball P. Chest.1995;108:43S-52S; Bartlett JG, et al.
Clin Infect Dis. 2000;31:347-382; Ray NF, et al. J Allergy Clin
Immunol. 1999;103:408-414.

randomized, controlled clinical trials in acute

bacterial rhinosinusitis suggests that Staphylo-
coccus aureus is a major pathogen, accounting
for 10% of cases.16 Whether or not this recent
identification of S aureus as a pathogen in acute
rhinosinusitis will alter treatment guidelines re-
mains to be seen. In contrast, anaerobes are less
commonly implicated, causing up to 9% of acute
rhinosinusitis in adults.12
Diagnosis of acute bacterial
versus viral rhinosinusitis
Sinus puncture with culture (maxillary sinus tap)
is the diagnostic reference standard for ABS.17 As
an alternative, endoscopically directed middle
meatal (EDMM) cultures may be considered.18
However, these tests are not practical routine

Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S

cri t eria f o r di st ing ui shing bac te ria l a nd v ira l in fect ions

Table 2

Clinical symptoms of RTIs of bacterial or viral etiology

Acute rhino- Acute bronchitis

ABS sinusitis (viral) ABECB (viral) Bacterial CAP Viral CAP

• Nasal drainage • Nasal discharge • Primary symptoms: • Dyspnea • Cough • Nonproductive

• Nasal congestion • Nasal congestion – Increased •C  ough often dry, • Purulent sputum cough (rule out
dyspnea nonproductive (nonproductive in atypical bacterial
• Facial pressure/ • Facial pressure
– Increased atypical cases) infection)
pain (especially • Cough • Cough may be
sputum volume • Gradual onset with
when unilateral productive of • Sudden onset
• Fever and chills – Increased sputum prodrome (malaise
and focused in purulence variably colored • Dyspnea
the region of a • Muscle aches and sputum and headache)
joint pain • May also exhibit: • Tachypnea
particular sinus • Cough onset within • Chest x-ray more
group) • Sore throat and – Sore throat • Tachycardia impressive than
2 days in 85% of
hoarseness and/or nasal • Pleuritic chest pain examination
• Purulent postnasal acute bronchitis
discharge within
drip • Spontaneously • Wheezing • Ill-appearing • Onset in fall or
past 5 days
• Hyposmia/anosmia resolves in 10-14 patient, especially winter
– Fever without • Chest pain
days with: • Wheezing more
• Cough other cause • Hoarseness
• Common in the fall, – Increased – Fever common in viral
• Fever • Constitutional – Fatigue
winter, and early causes
• Fatigue wheezing symptoms: – Abnormal breath
spring • Low-grade
– Increased cough – Fever sounds
• Maxillary dental temperature
pain – Elevated – Myalgia – Crackles
(<101.3º F)
respiratory or
• Ear fullness/ – Fatigue • Conjunctivitis
heart rate
pressure
• URTI that is
no better after
10 days, or
worsens after
5-7 days

ABECB, acute exacerbation of chronic bronchitis; ABS, acute bacterial rhinosinusitis; CAP, community-acquired pneumonia;
RTI, respiratory tract infection; URTI, upper respiratory tract infection.
Anon JB, et al. Otolaryngol Head Neck Surg. 2004;130(suppl 1):1-45; Anthonisen NR, et al. Ann Intern Med. 1987;106:196-204; Balter MS, et al. Can
Respir J. 2003;10(suppl B):3B-32B; Family Practice Notebook. www.fpnotebook.com/ENT189.htm. Accessed Jan 10, 2008.

procedures but rather, invasive, endoscopic- viral URTI whose symptoms have worsened after
directed cultures that require special equipment
and experience. Both are expensive. Therefore,
ABS is most commonly diagnosed by clinical
signs and symptoms.
Tabl e 2 lists the signs and symptoms typi-
cally associated with bacterial versus viral RTIs.
Diagnosis of ABS can be made in the presence of
the following 3 clinical criteria, which may have
moderate diagnostic sensitivity and specificity17:
• Purulent nasal discharge with either unilat-
eral or bilateral predominance
• Local pain with unilateral predominance
• Presence of pus in the nasal cavity.
ABS may also be diagnosed in patients with a
5 to 7 days or have not improved after 10 days
and are accompanied by some or all of the symp-
toms shown in Table 2 .12
Viral rhinosinusitis can cause the follow-
ing symptoms: coughing, facial pain, fever and
chills, muscle aches and joint pain, nasal conges-
tion and discharge, sore throat, and hoarseness.
Unlike bacterial rhinosinusitis, viral rhinosinus-
itis spontaneously resolves in 10 to 14 days and is
common in the fall, winter, and early spring.12,19
Although some clinical signs and symptoms
of bacterial and viral rhinosinusitis overlap, an-
tibiotics should be reserved primarily for indi-
viduals whose symptoms persist for 10 days or

S Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice


worsen after 5 to 7 days.12 However,
antibiotics can be used for patients with
moderately severe symptoms regard-
less of illness duration and for patients
with severe symptoms, such as fever or
significant pain or discomfort.20 The
color of the mucus is not a useful dis-
tinguishing feature in determining if an
infection is viral or bacterial because
discolored mucus is common in both
viral and bacterial rhinosinusitis. (Fur-
ther treatment recommendations are
discussed in “Treatment recommen-
dations for patients with common
respiratory tract infections with vari-
ables indicative of treatment failure”
on page S19.)
Acute bacterial exacerbation
of chronic bronchitis
Epidemiology and
burden of disease
Acute bacterial exacerbation of ABECB, acute exacerbation of chronic bronchitis; MRSA, methicillin-
resistant Staphylococcus aureus; MSSA, methicillin-susceptible
chronic bronchitis (ABECB) affects an Staphylococcus aureus.
estimated 13 million Americans (ap- Balter MS, et al. Can Respir J. 2003;10(suppl B):3B-32B; Habib MP, et al. Infect Dis
Clin Pract. 1998;7:101-109; Kahn JB, et al. Curr Med Res Opin. 2007;23:1-7.
proximately 4%-6% of adults [1995
figures]).21 These patients experience
an average of 3 ABECB episodes an-
nually, with one third each having <3, 3, and ≥4
episodes.22 In the 1990s, these acute episodes
accounted for about 12 million office visits an-
nually and for $200 million to $300 million in
medical costs.21
Viral pathogens are associated with only
30% of all AECBs, including influenza and
23
parainfluenza viruses, respiratory syncytial vi-
rus, rhinoviruses, and coronaviruses.23 Most ex-
acerbations of chronic bronchitis are bacterial in
nature, and 3 bacterial pathogens—H influen-
zae, S pneumoniae, and M catarrhalis—account
for 70% of all exacerbations and 85% to 95%
of bacterial exacerbations.23 A recent study by
Kahn et al evaluated patients with ABECB. These
Table 3
Bacterial pathogens isolated from patients with acute
bacterial exacerbation of chronic bronchitis
Kahn et al Habib et al
Pathogens (2007) N (%) (1998) N (%)
Typical ABECB pathogens 290 (44.0) 89 (49)
- Streptococcus pneumoniae 71 (10.8) 17 (9)
- Haemophilus influenzae 131 (19.9) 45 (25)
- Moraxella catarrhalis 88 (13.4) 27 (15)
Gram-negative organisms of note 145 (22.0) 58 (32)
- Enterobacteriaceae 95 (14.4) 34 (19)
- Pseudomonas spp 50 (7.6) 24 (13)
Gram-positive organisms of note
- Total Staphylococcus aureus 26 (3.9) 12 (7)
- Staphylococcus aureus (MSSA) 24 (3.6) —
- Staphylococcus aureus (MRSA) 2 (0.3) —
Other 169 (25.6) —
- Haemophilus parainfluenzae 134 (20.3) 22 (12)
- Other Haemophilus spp 26 (3.9) —
- Acinetobacter spp 9 (1.4) —
Other gram-negative spp 16 (2.4) —
Other gram-positive cocci 13 (2.0) —
3 pathogens were found in 46.2% (147/318) of
patients with less severe symptoms and 41.9%
(143/341) of patients with more severe symp-
toms.24 The authors also reported that gram-neg-
ative organisms were found in 22% of patients
(Enterobacteriaceae, 14.4%; Pseudomonas spp,
7.6%), and S aureus was found in 3.9% of pa-
tients (Table 3 ).24 These findings resemble those
of earlier studies.25,26
Diagnosis of acute bacterial exacerbation
of chronic bronchitis vs viral bronchitis
The Anthonisen classification system helps to
establish a diagnosis of ABECB. It uses 3 types of
exacerbations to identify patients likely infected

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C ri t eria f o r di st ing ui shing bac te ria l a nd v ira l in fect ions
with bacterial pathogens, based on the presence
of the clinical symptoms of increased dyspnea, spu-
tum volume, and sputum purulence (Tab le 2 ).26,27
In a type I exacerbation, all 3 symptoms are pres-
ent, whereas in type II and type III exacerbations,
2 symptoms and 1 symptom are present, respec-
tively.26 The Anthonisen classification is also
helpful in predicting antibiotic response (type I
being most predictive).26 Other symptoms may
also be present, such as sore throat and/or nasal
discharge within the past 5 days, fever without
other cause, and increased wheezing, cough, and
elevated respiratory or heart rate.26
The presence of green, purulent secretions is
especially predictive of a high bacterial load.26
As demonstrated by Balter et al, the presence less frequently implicated as causes of CAP.9 The
of these secretions was 99.4% sensitive and
77.0% specific for a high bacterial load in pa-
tients with a history of chronic obstructive pul-
monary disease.26
Patients with viral bronchitis present with
a wider range of signs and symptoms, includ-
ing dyspnea; a dry, nonproductive cough or a
cough that produces variably colored sputum;
cough onset within 2 days; wheezing; chest pain;
hoarseness; fever; myalgias; and fatigue.19
Community-acquired
pneumonia
Epidemiology and burden of disease
Pneumonia is the sixth leading cause of death
in the United States and ranks highest as the
cause of death among infectious diseases,28 with
an estimated 45,000 deaths annually (1997 fig-
ure).29 The increased death rate from pneumo-
nia observed over the past few years may result,
in part, from the aging of the population; some
of the higher mortality rate is attributed to pa-
tients ≥65 years of age.29 Signs and symptoms
independently associated with increased mortal-
ity include dyspnea, chills, altered mental status,
hypothermia or hyperthermia, tachypnea, and
hypotension (diastolic and systolic).29
S10 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice
CAP accounts for 500,000 hospitalizations
annually.29 An estimated 5% to 35% of patients
hospitalized with CAP have severe disease, which
accounts for 10% of all intensive care unit (ICU)
admissions.30 In 1998, Niederman et al calculat-
ed the cost of health care resource utilization for
CAP to be $4.8 billion for patients ≥65 years and
$3.6 billion for patients <65 years.31
CAP is caused primarily by bacterial patho-
gens (Table 1 ). S pneumoniae is the most com-
mon cause of CAP (20%-60% of all episodes),
followed by H influenzae (3%-10% of all
episodes) (1990 figures).9,28 Atypical bacterial
pathogens, such as Mycoplasma pneumoniae,
Chlamydia pneumoniae, and Legionella spp, are
percentage of viral CAP (1% in the United States)
is negligible.32 Because bacterial pathogens are
predominant in CAP, treatment guidelines from
the American Thoracic Society and the Infectious
Diseases Society of America recommend antibi-
otic treatment for all patients.28,33
Diagnosis of acute community-acquired
pneumonia
CAP is indicated by the onset of cough, sputum
production, and/or dyspnea in nonhospitalized
patients. Fever and abnormal breath sounds and
crackles on auscultation further support a diag-
nosis of CAP. In immunosuppressed or elderly
patients, respiratory symptoms may be absent;
patients with CAP may present with symptoms
such as confusion, malaise, or tachypnea. Stan-
dard posteroanterior and lateral chest x-rays are
strongly recommended to confirm a diagnosis
of CAP.28 In bacterial CAP, coughing produces
purulent sputum, whereas a nonproductive
cough is more common in viral CAP or in pneu-
monia caused by atypical pathogens, such as
M pneumoniae and Legionella spp.19 In addi-
tion, in bacterial CAP a sudden onset is com-
mon, compared with a gradual onset in viral
CAP.19 Further differentiating signs and symp-
toms are shown in Table 2 .
Conclusion
Acute rhinosinusitis, AECB, and CAP are com-
monly encountered infectious diseases that vary
in the incidence of viral and bacterial origin. Most
cases of rhinosinusitis are viral in origin, whereas
AECB and CAP commonly result from bacterial
infection. Clinicians must be able to differenti-
ate viral and bacterial RTIs before they reach for
their prescription pads. Inappropriate antibiotic
prescribing leads to unnecessary drug-related
adverse events, excessive medication costs, and
the development of antibiotic resistance. Practi-
tioners must resist the various pressures placed
on them to prescribe antibiotics inappropriately
and instead determine the etiology of these RTIs
for optimal patient care. n

References

1. Avorn J, Solomon DH. Cultural and eco-
nomic factors that (mis)shape antibiotic use:
the nonpharmacologic basis of therapeutics.
Ann Intern Med. 2000;133:128-135.
2. Steinman MA, Gonzales R, Linder JA, et
al. Changing use of antibiotics in community-
based outpatient practice, 1991-1999. Ann
Intern Med. 2003;138:525-533.
3. Gonzales R, Malone DC, Maselli JH, et al.
Excessive antibiotic use for acute respiratory
infections in the United States. Clin Infect Dis.
2001;33:757-762.
4. Fendrick AM, Monto AS, Nightengale B, days each year. www.medicalnewstoday.com/
et al. The economic burden of non-influenza-
related viral respiratory tract infection in the
United States. Arch Intern Med. 2003;163: al. Etiology and antimicrobial therapy of acute
487-494.
5. Nouwen JL. Controlling antibiotic use and
resistance. Clin Infect Dis. 2006;42:776-777.
6. Livermore DM. Minimising antibiotic resis-
tance. Lancet. 2005;5:450-459.
7. Bronzwaer SL, Cars O, Buchholz U, et al.
A European study on the relationship between
antimicrobial use and antimicrobial resistance.
Emerg Infect Dis. 2002;8:278-282.
8. Sahm DF, Benninger MS, Evangelista AT, et
al. Antimicrobial resistance trends among sinus
isolates of Streptococcus pneumoniae in the
United States (2001-2005). Otolaryngol Head
Neck Surg. 2007;136:385-389.
9. Brown SD, Rybak MJ. Antimicrobial
susceptibility of Streptococcus pneumoniae,
Streptococcus pyogenes and Haemophi-
lus influenzae collected from patients across
the USA, in 2001-2002, as part of the Jan 10, 2008.
PROTEKT US study. J Antimicrob Chemother.
2004;54(suppl 1):i7-15.
10. Centers for Disease Control and Preven-
tion. Active Bacterial Core Surveillance (ABCs)
Report Emerging Infections Program Network,
Streptococcus pneumoniae. www.cdc.gov/
ncidod/dbmd/abcs/survreports/spneu03.pdf.
Accessed Jan 23, 2008.
11. Gwaltney JM Jr. Acute community-ac-
quired sinusitis. Clin Infect Dis. 1996;23: acerbations of chronic bronchitis. Semin Respir
1209-1225.
12. Anon JB, Jacobs MR, Poole MD, et al, for
the Sinus and Allergy Health Partnership. An-
timicrobial treatment guidelines for acute bac-
terial rhinosinusitis. Otolaryngol Head Neck
Surg. 2004;130(suppl 1):1-45.
13. Ray NF, Baraniuk JN, Thamer M, et al.
Healthcare expenditures for sinusitis in 1996:
contributions of asthma, rhinitis, and other
airway disorders. J Allergy Clin Immunol.
1999;103:408-414.
14. Uhl J, Manko S. Sinusitis, bronchitis ing efficacy and safety of oral levofloxacin and
account for more than 30 million missed work-
articles/15277.php. Accessed Jan 16, 2008.
15. Hamory BH, Sande MA, Sydnor A Jr, et
maxillary sinusitis. J Infect Dis. 1979;139:197-
202.
16. Payne SC, Benninger MS. Staphylococcus
aureus is a major pathogen in acute bacterial
rhinosinusitis: a meta-analysis. Clin Infect Dis.
2007;45:e121-127. Epub 2007 Oct 11.
17. Agency for Health Care Policy and Re-
search. Diagnosis and treatment of acute
bacterial rhinosinusitis: summary. Evidence Re-
port/Technology Assessment AHCPR Pub No.
99-E015, 1999.
18. Benninger MS, Payne SC, Ferguson BJ,
et al. Endoscopically directed middle meatal 29. Bartlett JG, Dowell SF, Mandell LA, et al.
cultures versus maxillary sinus taps in acute bac-
terial maxillary rhinosinusitis: a meta-analysis.
Otolaryngol Head Neck Surg. 2006;134:3-9.
19. Family Practice Notebook. Rhinosinusitis.
www.fpnotebook.com/ENT189.htm. Accessed
20. Hickner JM, Bartlett JG, Besser RE, et al.
Principles of appropriate antibiotic use for
acute rhinosinusitis in adults: background. Ann
Intern Med. 2001;134:498-505.
21. Sethi S. Infectious exacerbation of chronic
bronchitis: diagnosis and management. J An-
timicrob Chemother. 1999;43(suppl A):97-
105.
22. Niederman MS. Antibiotic therapy of ex-
Infect. 2000;15:59-70.
23. Ball P. Epidemiology and treatment of
chronic bronchitis and its exacerbations. Chest.
1995;108:43S-52S.
24. Kahn JB, Khashab AM, Ambrusz M. Study
entry microbiology in patients with acute
bacterial exacerbations of chronic bronchitis
in a clinical trial stratifying by disease severity.
Curr Med Res Opin. 2007;23:1-7.
25. Habib MP, Gentry LO, Rodriguez-Gomez
G, et al. Multicenter, randomized study compar-
cefaclor in treatment of acute bacterial exacer-
bations of chronic bronchitis. Infect Dis Clin
Pract. 1998;7:101-109.
26. Balter MS, La Forge J, Low DE, et al. Ca-
nadian guidelines for the management of acute
exacerbations of chronic bronchitis. Can Respir
J. 2003;10(suppl B):3B-32B.
27. Anthonisen NR, Manfreda J, Warren CPW,
et al. Antibiotic therapy in exacerbations of
chronic obstructive pulmonary disease. Ann In-
tern Med. 1987;106:196-204.
28. Niederman MS, Mandell LA, Nanuet A,
et al. Guidelines for the management of adults
with community-acquired pneumonia: diagno-
sis, assessment of severity, antimicrobial thera-
py, and prevention. Am J Respir Crit Care Med.
2001;163:1730-1754.
Practice guidelines for the management of com-
munity-acquired pneumonia in adults. Clin In-
fect Dis. 2000; 31:347-382.
30. de Castro FR, Torres A. Optimizing treat-
ment outcomes in severe community-acquired
pneumonia. Am J Respir Med. 2003;2:39-54.
31. Niederman MS, McCombs JS, Unger AN,
et al. The cost of treating community-acquired
pneumonia. Clin Ther. 1998;20:820-837.
32. File TM. Community-acquired pneumonia.
Lancet. 2003;362:1991-2001.
33. Mandell LA, Wunderink RG, Anzueto A,
et al. Infectious Diseases Society of America/
American Thoracic Society consensus guide-
lines on the management of community-
acquired pneumonia in adults. Clin Infect Dis.
2007;44(suppl 2):527-572.

Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S11
 Available at www.jfponline.com

Patient variables associated

with treatment failure in respiratory
tract infections
Hans H. Liu, MD • Robert E. Siegel, MD

Key Points
o Without effective antibiotic
treatment, bacterial respiratory tract
infections may worsen and spread,
resulting in potentially serious health
consequences and increased costs
to the patient.
o Patient variables associated
with treatment failure include
comorbidities and infection with a
resistant pathogen as well as less
obvious social factors that may
complicate the course of disease.
o Treatment failure may subject
patients to prolonged discomfort,
treatment dissatisfaction, missed
work, hospitalization, increased
costs from additional anti-infective
treatments, or other negative results.
o When selecting antibiotic therapy,
clinicians should consider the
complete clinical and social profile
of a patient with respiratory tract
infections.
C
ertain factors predispose some patients with respira-
tory tract infections (RTIs) to treatment failure. In
“Is it bacterial or viral? Criteria for distinguishing
bacterial and viral infections” (see page S5), the authors de-
scribed strategies to distinguish bacterial from viral RTIs—a
crucial step in appropriate antibiotic prescribing. Clinicians
also need to be aware of individual patient circumstances that
may negatively affect treatment. This article provides a clini-
cal algorithm based on current treatment guidelines and the
combined clinical experience of a multidisciplinary consensus
group. We hope this tool will help clinicians to identify pa-
tients with clinical and social factors indicative of treatment
failure in common bacterial RTIs, and avoid the potential
consequences of inappropriate first-line treatment.
Patient variables that affect treatment
outcomes
When a patient presents with an RTI, a complete assessment
provides the first step in identifying variables that may affect
treatment outcomes. Some of the more obvious questions that
should be posed include:
• Does the patient look “toxic” or have abnormal vital
signs? If so, is the patient medically unstable, indicating
the need for hospitalization?
• Does the patient have comorbidities such as diabetes,
human immunodeficiency virus (HIV), cardiovascular

Disclosures: Dr Liu has disclosed that he is on the speakers bureau of Aventis Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol-
Myers Squibb Company, Cubist Pharmaceuticals, GlaxoSmithKline, Merck & Co., Inc., Ortho-McNeil-Janssen Pharmaceuticals, Inc, Pfizer Inc,
Purdue Pharma, Oscient Pharmaceuticals Corporation, and Wyeth Pharmaceuticals. Dr Siegel has disclosed that he has served as a consultant
for and on the speakers bureau of Boehringer Ingelheim, GlaxoSmithKline, Ortho-McNeil-Janssen Pharmaceuticals, Inc, and Pfizer Inc.

S12 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice
 disease, chronic obstructive pulmonary disease
(COPD), or underlying malignancy, which are
likely to affect the course of the RTI?
• Does the patient smoke or abuse alcohol?
• Is the patient older than 65 years and/or have
poor functional status?
A complete patient profile requires further prob-
ing and history taking, especially for new patients.
Clinical factors
list the clinical variables associated
Tabl e s 1 - 3
with treatment failure specific to patients with
3 common RTIs: acute bacterial rhinosinusitis
(ABS), acute bacterial exacerbation of chronic
bronchitis (ABECB), and community-acquired
pneumonia (CAP). Some variables overlap in sistant pathogens (Table 1 ).2-4 Patients who have
all 3 RTIs, such as recent antibiotic use and an
immunosuppressive illness or treatment with
an immunosuppressive agent (Fig ur e 1 ). Other
variables overlap in 2 RTIs: in ABECB and CAP, with ABS who had been treated with antibiotics
advanced age is an important clinical indicator
of treatment failure; and in ABS and CAP, malig-
nancies and contact with children in day care can
complicate treatment. Other variables are specific
to the individual disease.
Social factors
In addition to medical considerations, the clini-
cian’s complete assessment may discover less-
obvious patient variables, such as complicating
social factors. These factors may affect the course
of the RTI and influence the clinician’s treatment
decisions (F ig u r e 2 ). For example, those who live
alone (especially those with poor functional status
or elderly patients), may find it difficult to adhere
to outpatient treatments; they also may not have
a sufficient family or social network to meet their
needs during an illness. Such patients may be lost
to further follow-up, and appropriate initial an-
tibiotic therapy is especially important for them.
The alternative treatment option for these patients
is often hospital admission.1
Patients may also have stressful work sched-
ules and may travel frequently. They may not be
Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008
able to afford missed workdays, with the poten-
tial consequences of lost pay, missed deadlines,
and an increased workload when they eventually
return to work. In addition, patients may have
family responsibilities, such as the care of young
children or elderly family members, or they may
have busy social lives that they are unwilling to
curtail for long. These patients require rapid res-
olution of their symptoms through appropriate
first-line therapy, both for medical reasons and to
accommodate their lifestyles.
Acute bacterial rhinosinusitis
Clinical risk factors identified in the rhinosinus-
itis guidelines focus on anticipating antibiotic-re-
received antibiotics within the prior 4 to 6 weeks
are especially at risk of acquiring resistant patho-
gens.2 One small study (N = 20) evaluated patients
as early as 6 months prior to diagnosis. Follow-up
showed a significantly higher recovery of resistant
organisms from these patients.4 Penicillin-nonsus-
ceptible pneumococcal infections are associated
with comorbid conditions such as organ trans-
plantation, HIV infection, asplenia, malignancies,
and sickle cell disease in patients who receive peni-
cillin prophylaxis.3 In addition, in patients with si-
nusitis, smoking has been identified as a risk factor
for infection with resistant strains.4
Other patients at risk of treatment failure for
ABS have moderate or severe disease. Moderate
disease is characterized by more severe symp-
toms, but this remains a clinical judgment. Symp-
toms associated with ABS include nasal drainage
and congestion, facial pain or pressure, postna-
sal drip, fever, cough, and fatigue, among others.
These patients are more likely to experience dis-
comfort and may also have a reduced tolerance
for treatment failure.2
Acute bacterial exacerbation of chronic
bronchitis and treatment failure
In ABECB, variables associated with treatment
S13
Pat ie n t variabl es in rt i t r eatment fai lure

FIGURE 1

Where complicating patient variables overlap in disease states

ABS: Risk factors for resistant

organisms
• Smoking
• Severity of symptoms (more discomfort)
associated with reduced tolerance for
treatment failure

ABS and CAP

• Contact with
children in
day care
CAP: Risk factors for • Malignancies ABECB: Risk factors
resistant pathogens
ABS, ABECB, for treatment failure or
• Alcoholism and CAP resistant pathogens
• Multiple medical conditions • Recent antibiotic use • >4 exacerbations/year
• Immunosuppressive illness • Immunosuppressive • Cardiac disease
• Contact with children in day care illness/treatment* • History of previous
pneumonia
CAP: Increased risk factors for a
complicated course of CAP CAP and ABECB • Use of home oxygen
• Temperature >38.3ºC • Advanced age/older • FEV1 <50% predicted
patients (>65 years
• High-risk etiologies (S pneumoniae, S aureus,
of age)
enteric gram-negative bacteria, P aeruginosa)
ABECB: Factors that increase the
• Increased risk for mortality cost of treatment failure
— At least 2 of the following: • Cardiac disease
- Respiratory rate ≥30/minute • Significant comorbidity
- Blood urea nitrogen ≥7.0 mmol/L • Chronic corticosteroid administration
(>19.1 mg/dL)
• Frequent purulent exacerbations of COPD
- Diastolic blood pressure ≤60 mm Hg
• Malnutrition
- Mental confusion
• Severely impaired underlying lung function
• Chronic mucous hypersecretion
• Use of supplemental oxygen
• Generalized debility

*Recent systemic corticosteroid therapy or cancer chemotherapy, chronic oral steroid use, sickle cell disease, HIV infection, or asplenia.

ABECB, acute bacterial exacerbation of chronic bronchitis; ABS, acute bacterial rhinosinusitis; CAP, community-acquired
pneumonia; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; HIV, human
immunodeficiency virus.
Anon JB, et al. Otolaryngol Head Neck Surg. 2004;130(suppl 1):1-45; Balter MS, et al. Can Respir J. 2003;10(suppl B):3B-32B; Brook I, et al. Ann
Otol Rhinol Laryngol. 1999;108:645-647; Brunton S, et al. Am J Manag Care. 2004;10:689-696; de Castro FR, et al. Am J Respir Med. 2003;2:39-54;
Grossman RF. Chest. 1997;112:310S-313S; Grossman RF. Semin Respir Infect. 2000;15:71-81; Jacobs MR. Am J Med. 2004;117(suppl 3A):3S-15S;
Mandell LA, et al. Clin Infect Dis. 2003;37:1405-1433; Niederman MS. Semin Respir Infect. 2000;15:59-70; Niederman MS, et al. Am J Respir Crit
Care Med. 2001;163:1730-1754.

failure may be loosely categorized as those relat- both categories (Table 2 ).

ing to clinical issues (eg, infection with a resistant Similar to ABS, variables associated with
pathogen) or those resulting in increased costs. treatment failure in ABECB include recent anti-
Although the rationales behind the 2 categories biotic use and significant comorbidities, such as
are different, many similar variables are present in cardiac disease, which can increase the risk of

S14 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice
FIGURE 2

Assessment of factors that may affect RTI disease course

and consequences of inappropriate treatment of RTIs

Assess patient/vital signs

Healthy Looks sick (“toxic”) /abnormal vital

signs/hospitalization required

Stable Unstable Hospitalization

Outpatient

Consequences of inappropriate treatment Risk factors for disease progression present? Yes
• Hospitalization • Significant comorbidity
• Disease progression –Uncontrolled diabetes, HIV, underlying malignancy,
• Need for ICU/ventilator COPD/emphysema, cardiovascular disease/heart
• Exacerbation of underlying disease failure, immunosuppression
• Sepsis (eg, phlebitis at IV site)/bacteremia • Cigarette smoking
• If admitted, potential for nosocomial infection • Alcohol abuse
(eg, Clostridium difficile) • Poor functional status
• Age >65

No

Consequences of inappropriate treatment Complicating social factors present? Yes

• Missed opportunities (work, family, special events) • May be lost to follow-up
• Frustration level increases (will patient be able to make follow-up • Patient who lives alone
appointment; will it be a follow-up by phone call?) • Patients with critical jobs
• Patient may go to urgent care center (increased cost, inconvenience, • Patients who travel
relationship between doctor and patient suffers) • Patients with family obligations
• If follow-up by phone call, missing important facts such as allergies, (eg, caregivers for children or elderly persons)
drug interactions, etc, doctor may order an inappropriate medication

No

Consequences of inappropriate treatment At risk for infection with a resistant pathogen? Yes
• Prolonged suffering • Previous antibiotic use
• Similar consequences to other groups • Exposure to children in day care (CAP)
• Dissatisfaction, missed work, etc.
• Extended treatment course with antibiotic leads to unrecognized
treatment failure because doctor believes patient needs No
repeated antibiotic course
• Patient exposed to further development of bacterial resistance

Mild MODERATE (at risk)

Flow chart showing variables associated with treatment failure and the potential consequences of inappropriate treatment for
common respiratory infections

CAP, community-acquired pneumonia; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus;
ICU, intensive care unit; RTI, respiratory tract infection.
Balter MS, et al. Can Respir J. 2003;10(suppl B):3B-32B; Brook I, et al. Ann Otol Rhinol Laryngol. 1999;108:645-647; de Castro FR, et al. Am J Respir
Med. 2003;2:39-54; Grossman RF. Semin Respir Infect. 2000;15:71-81; Jacobs MR. Am J Med. 2004;117(suppl 3A):3S-15S; Niederman MS, et al. Am
J Respir Crit Care Med. 2001;163:1730-1754.

Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S15
Pat ie n t variabl es in rt i t r eatment fai lure

Table 1
treatment failure more than 2-fold.5,6 For patients
Variables associated with with ABECB, the severity of the underlying lung
treatment failure in ABS disease—as indicated by use of home oxygen,
Risk factors for resistant pathogens FEV1 level, number of exacerbations per year, or
• Recent antibiotic use history of pneumonia—and chronic oral steroid
• Organ transplantation, HIV infection, asplenia, use are also important risk factors for treatment
malignancies, and sickle cell disease in patients who
receive penicillin prophylaxis
failure.5-10
• Smoking Treatment failure in ABECB has been shown
to result in increased use of health care resources
Reduced tolerance for treatment failure
caused by additional physician visits, further diag-
• More severe symptoms (more discomfort)
nostic tests, and repeated antibiotic treatments.5,6
ABS, acute bacterial rhinosinusitis; HIV, human
immunodeficiency virus.
Significant comorbidity, such as cardiac disease,
Anon JB, et al. Otolaryngol Head Neck Surg. 2004;130(suppl 1):1-45; chronic corticosteroid administration, severely
Brook I, et al. Ann Otol Rhinol Laryngol. 1999;108:645-647; Jacobs
MR. Am J Med. 2004;117(suppl 3A):3S-15S. impaired underlying lung function, use of supple-
mental oxygen, frequent purulent exacerbations
of COPD, malnutrition, advanced age, general-
Table 2
ized debility, and chronic mucous hypersecretion
Variables associated with (Table 2 ) all increase the costs associated with
treatment failure in ABECB treatment failure and hospitalization.5,6
Risk factors for treatment failure
• Recent antibiotic use (in the past 3 months)
Community-acquired pneumonia:
• Cardiac disease
Resistant pathogens and other factors
• Severe underlying lung disease
Because the prognosis of CAP can range from
– Use of home oxygen
– FEV1 <50% predicted
rapid symptomatic recovery without functional
– ≥4 exacerbations/year impairment to serious morbid complications and
– History of previous pneumonia death, it is especially important to identify pa-
• Chronic oral steroid use tients who are at risk of treatment failure.11 As
Factors that increase the cost of treatment failure
with other RTIs, acquisition of resistant patho-
• Significant comorbidity gens in CAP is an important predictor of treat-
– Cardiac disease ment failure. Additional predictors of treatment
• Chronic corticosteroid administration failure in CAP, stratified by level of importance,
• Severely impaired underlying lung function are shown in Table 3 .3,11-15
• Use of supplemental oxygen As seen in ABS and ABECB, one of the most
• Frequent purulent exacerbations of COPD important risk factors for infection with a re-
• Malnutrition sistant organism is recent antibiotic therapy,
• Advanced age
including β-lactam therapy within the past 3
• Generalized debility
months.4,12,13 Other modifying factors that in-
• Chronic mucous hypersecretion
crease the risk of infection with drug-resistant
ABECB, acute bacterial exacerbation of chronic bronchitis; pneumococci include age >65 years, alcoholism,
COPD, chronic obstructive pulmonary disease; FEV1, immunosuppressive illness requiring long-term
forced expiratory volume in 1 second.
Balter MS, et al. Can Respir J. 2003;10(suppl B):3B-32B; Brunton S,
corticosteroids, multiple medical comorbidities,
et al. Am J Manag Care. 2004;10:689-696; Dewan NA, et al. Chest. and exposure to a child in day care.12 Finally,
2000;117:662-671; Grossman RF. Chest. 1997;112(6 suppl):310S-313S;
Grossman RF. Semin Respir Infect. 2000;15:71-81; Niederman MS. organ transplantation, HIV, asplenia, and malig-
Semin Respir Infect. 2000;15:59-70.
nancies are comorbid conditions associated with

S16 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice

pneumococcal infections that are not susceptible
to penicillin.3
A limited but significant number of patients
initially believed to have mild pneumonia will
develop more severe CAP and will require hos-
pitalization. Risk factors for complicated CAP
include age >65 years, comorbid illnesses, tem-
perature >38.3º C, immunosuppression due to
continuous corticosteroid use or cancer chemo-
therapy, and the presence of high-risk etiologies
such as Staphylococcus aureus or enteric gram-
negative bacteria.14
Numerous prognostic factors for death from
CAP have been identified.14 The risk of treatment
failure increases proportionally with the number of
risk factors the patient has.14 Signs and symptoms
that are independently associated with increased
CAP mortality are dyspnea, chills, altered mental
status, hypothermia or hyperthermia, tachypnea,
and diastolic or systolic hypotension.14,16 The risk
of death may also be significantly associated with
the identity of the infecting pathogen; mortality
was found to be highest for patients with pneumo-
nia caused by Pseudomonas aeruginosa, Klebsiella
species, Escherichia coli, or S aureus.15,16
Potential consequences of treatment
failure in patients with RTIs
Treatment failure in patients with comorbidi-
ties often leads to exacerbation of an underly-
ing disease state, such as diabetes, or worsening
of the infection to the point that hospitalization
is required. Although ABS rarely leads to hospi-
talization, severe lower RTIs such as ABECB or
CAP can become serious enough that the patient
must be hospitalized, which in turn can intro-
duce further challenges.5,12,13
A multidisciplinary group investigating the
consequences of antibiotic treatment failure in
RTIs found that approximately 10% of patients
with RTIs failed treatment with a macrolide an-
tibiotic.17 This resulted in increased health care
utilization, including hospitalizations, emergency
Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008
Table 3
Risk factors for treatment failure in CAP
Risk factors for resistant pathogens
• Recent antibiotic use
• Older patients (age >65 years)
• Contact with children in day care
• Alcoholism
• Multiple medical comorbidities
• Immunosuppressive illness
• Increased risks for resistant S pneumoniae include
malignancies, HIV infection, asplenia, and patients with
sickle cell disease who receive penicillin prophylaxis
Increased risks for a complicated course of CAP
• Age >65 years
• Comorbid illness
• Temperature >38.3ºC
• Immunosuppression (recent systemic corticosteroid
therapy or cancer chemotherapy)
• High-risk etiologies (S pneumoniae, S aureus, enteric
gram-negative bacteria, P aeruginosa)
Increased risks for mortality
• At least 2 of the following:
- Respiratory rate ≥30/minute
- Blood urea nitrogen >7.0 mmol/L (>19.1 mg/dL)
- Diastolic blood pressure ≤60 mm Hg
• Dyspnea
• Chills
• Altered mental status
• Hypothermia or hyperthermia
• Tachypnea
• Diastolic or systolic hypotension
• High-risk etiologies (P aeruginosa, Klebsiella spp,
E coli, or S aureus)
CAP, community-acquired pneumonia; HIV, human
immunodeficiency virus.
Bartlett JG, et al. Clin Infect Dis. 2000;31:347-382; de Castro FR, et al.
Am J Respir Med. 2003;2:39-54; Fine MJ, et al. JAMA. 1996;275:134-
141; Jacobs MR. Am J Med. 2004;117(suppl 3A):3S-15S; Mandell LA,
et al. Clin Infect Dis. 2003;37:1405-1433; Niederman MS, et al. Am J
Respir Crit Care Med. 2001;163:1730-1754.
department visits, and additional office visits.17
Repeated courses of antibiotics for hospitalized
patients also put these patients at a higher risk
of infection with resistant organisms, a situation
that can have socioeconomic as well as clinical
consequences.
S17
Pat ie n t variabl es in rt i t r eatment fai lure

Conclusion agent may lead to an improved clinical outcome.

RTI is one of the most common reasons that It may also reduce the overall costs of treatment,
patients seek medical attention. When patients particularly when it prevents complications
present with variables associated with treatment of the infection, respiratory failure, and hos-
failure, the clinician should take extra care to pital admission.6 It is therefore crucial to initi-
reduce the impact of these infections on patients’ ate appropriate empiric antibiotic therapy in a
health and normal functioning. timely fashion. Treatment recommendations for
After the clinician has determined that the patients at risk of treatment failure are presented
etiology of the RTI is bacterial and not viral, in the next article in this supplement, by Basri et
treatment with an appropriate antimicrobial al (see page S19). n

References

1. Marrie TJ, Huang JQ. Low-risk patients
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2. Anon JB, Jacobs MR, Poole MD, et al, for
the Sinus and Allergy Health Partnership. An-
timicrobial treatment guidelines for acute bac-
terial rhinosinusitis. Otolaryngol Head Neck
Surg. 2004;130(suppl 1):1-45.
3. Jacobs MR. Streptococcus pneumoniae:
epidemiology and patterns of resistance. Am
J Med. 2004;117(suppl 3A):3S-15S.
4. Brook I, Gober AE. Resistance to antimi-
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1999;108:645-647.
5. Balter MS, La Forge J, Low DE, et al.
Canadian guidelines for the management of
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6. Grossman RF. Cost-effective therapy for
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Semin Respir Infect. 2000;15:71-81.
7. Grossman RF. Guidelines for the treatment
of acute exacerbations of chronic bronchitis.
Chest. 1997;112:310S-313S.
8. Brunton S, Carmichael BP, Colgan R, et
al. Acute exacerbation of chronic bronchitis: immunocompetent adults. Clin Infect Dis.
a primary care consensus guideline. Am J
Manag Care. 2004;10:689-696.
9. Niederman MS. Antibiotic therapy of
exacerbations of chronic bronchitis. Semin
Respir Infect. 2000;15:59-70.
10. Dewan NA, Rafique S, Kanwar B, et al.
Acute exacerbation of COPD: factors asso-
ciated with poor treatment outcome. Chest.
2000;117:662-671.
11. Bartlett JG, Dowell SF, Mandell LA, et
al. Practice guidelines for the management of
community-acquired pneumonia in adults.
Clin Infect Dis. 2000;31:347-382.
et al. Guidelines for the management of adults
with community-acquired pneumonia: diag-
nosis, assessment of severity, antimicrobial
therapy, and prevention. Am J Respir Crit Care
Med. 2001;163:1730-1754.
13. Mandell LA, Bartlett JG, Dowell SF, et al.
Update of practice guidelines for the manage-
ment of community-acquired pneumonia in
2003;37:1405-1433.
14. de Castro FR, Torres A. Optimizing treat-
ment outcomes in severe community-acquired
pneumonia. Am J Respir Med. 2003;2:39-54.
15. Fine MJ, Smith MA, Carson CA, et al.
Prognosis and outcomes of patients with com-
munity-acquired pneumonia: a meta-analysis.
JAMA. 1996;275:134-141.
16. Ball P. Epidemiology and treatment of
chronic bronchitis and its exacerbations.
Chest. 1995;108:43S-52S.
17. Wu JH, Howard DH, McGowan JE Jr,
et al. Patterns of health care resource utilization
after macrolide treatment failure: results from
a large, population-based cohort with acute
sinusitis, acute bronchitis, and community-
acquired pneumonia. Clin Ther. 2004;26:
2153-2162.

S18 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice
 Available at www.jfponline.com

Treatment recommendations for patients

with common respiratory tract infections with
variables indicative of treatment failure
Raymond S. Basri, MD • David A. Weiland, MD • Greg L. Ledgerwood, MD

F
or patients with respiratory tract infections (RTIs), anti-
microbial treatment is prescribed to decrease the bacte-
Key Points
rial burden, return the patient to baseline condition, and o Treatment with an appropriate
antimicrobial agent significantly
reduce the risk of the patient progressing to a more severe in-
decreases the bacterial burden
fection.1 Although agents from several antimicrobial classes are and reduces the risk of a patient
approved to treat these infections, certain patient and pathogen progressing to a more severe
factors will limit the selection of appropriate therapy. It is criti- infection.
cally important to identify risk factors that may put patients at o When evaluating the use of
risk of treatment failure because these patients may require more antibiotics, practitioners should
aggressive therapy to achieve the desired treatment outcome and consider such factors as the local
resistance patterns of common
to minimize the potential development of severe complications.
respiratory pathogens, the
In “Patient variables associated with treatment failure in likelihood of infection with a
respiratory tract infections” (see page S12), Liu and Siegel iden- resistant organism, and the
tified variables associated with treatment failure, which play potential for treatment failure.
critical roles in selection of antimicrobial therapy. Primary care o Recent antibiotic use is a risk factor
practitioners typically provide empirical RTI treatment; there- for treatment failure.
fore, the optimal agent should provide coverage for all poten- o For patients with risk factors
tial pathogens. The bacterial species most commonly isolated predictive of treatment failure,
from patients with RTIs include Streptococcus pneumoniae, β-lactams (usually in combination
with a β-lactamase inhibitor or a
Haemophilus influenzae, and Moraxella catarrhalis. In patients
macrolide) and fluoroquinolones
with acute bacterial rhinosinusitis (ABS) and acute bacterial are most commonly recommended.
exacerbation of chronic bronchitis (ABECB) (Tab le 1 ), these 3
pathogens account for approximately 80% of cases, although
various other gram-positive and gram-negative species can
play an important role.2-5 In patients with community-acquired
pneumonia (CAP), studies of sputum cultures indicate that
S pneumoniae infections predominate, although infection with

Disclosures: Dr Basri is a consultant for and serves on the speakers bureau of Daiichi-Sankyo, King Pharmaceuticals, Novartis Pharmaceuticals,
Ortho-McNeil-Janssen Pharmaceuticals, Inc, Pfizer Inc, and sanofi-aventis; is a shareholder of Genentech, Inc, King Pharmaceuticals, Merck &
Co., Inc., Ortho-McNeil-Janssen Pharmaceuticals, Inc, Pfizer Inc, Novartis Pharmaceuticals, and Schering-Plough. Dr Weiland has served as a
consultant for and is on the speakers bureau of Abbott Laboratories, Ortho-McNeil-Janssen Pharmaceuticals, Inc, Pfizer Inc, and sanofi-aventis. Dr
Ledgerwood has served as a consultant for Alcon, ALTANA Pharma, Astra-Zeneca, GlaxoSmithKline, MedPointe, Inc, and Ortho-McNeil-Janssen
Pharmaceuticals, Inc; and is on the speakers’ bureau of Alcon, Astra-Zeneca, and GlaxoSmithKline.

Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S19
Tre at m e n t fo r RT I pat i ents pr one to t reatment failur e

Table 1
States. Results from this study have
Bacterial distribution associated with RTIs shown a sequential increase in penicil-
Prevalence (%)
lin- and azithromycin-resistant S pneu-
moniae over successive respiratory
Pathogen ABS ABECB CAP seasons. In 2004 and 2005, 28.8% of
Streptococcus pneumoniae 20-43 3-25 20-60 S pneumoniae isolates were resistant to
Haemophilus influenzae 22-35 14-36 3-10
azithromycin compared with 23% in
1998 and 1999.8 Penicillin resistance
Moraxella catarrhalis 2-10 7-21 —
(minimum inhibitory concentration
Staphylococcus aureus 0-8 3-20 3-5
[MIC] ≥2 mcg/mL) in S pneumoniae
Streptococcus spp 3-9 — — has also remained at elevated levels,
Anaerobes 0-9 — — with 15.6% of isolates exhibiting
Pseudomonas spp — 1-15 — high-level resistance and 19.3% exhib-
iting intermediate resistance in 2004-
Haemophilus parainfluenzae — 2-28 —
2005.8 Resistance to levofloxacin has
Enterobacteriaceae spp — 5-33 —
been rare and sporadic over the years,
Mycoplasma pneumoniae — — 1-6 with more than 99% of S pneumoniae
Chlamydia pneumoniae — — 4-6 isolates remaining susceptible to this
Legionella spp — — 2-8 agent in 2005.8 Among other common
respiratory tract pathogens, H influen-
Gram-negative bacteria — — 3-10
zae and M catarrhalis are frequently
ABECB, acute bacterial exacerbation of chronic bronchitis; ABS, acute resistant to β-lactams, such as ampicil-
bacterial rhinosinusitis; CAP, community-acquired pneumonia. RTI,
respiratory tract infection. lin.9 Fortunately, these pathogens re-
Anon JB, et al. Otolaryngol Head Neck Surg. 2004;130(suppl 1):1-45; Balter MS, main susceptible to other commonly
et al. Can Respir J. 2003;10(suppl B):3B-32B; Bartlett JG, et al. N Engl J Med.
1995;333:1618-1624; Mandell LA, et al. Clin Infect Dis. 2007;44(suppl 2):S27- used agents, such as the macrolides
S72; Niederman MS, et al. Am J Respir Crit Care Med. 2001;163:1730-1754.
and fluoroquinolones. Nonetheless,
these findings emphasize that antimi-
crobial resistance rates, particularly for
Staphylococcus aureus, H influenzae, and other S pneumoniae, are elevated for certain agents and
enteric gram-negatives is also common (Tab le 1 ). may affect appropriate therapeutic selection.
Atypical pathogens, such as Mycoplasma pneumoni-
ae, Chlamydia pneumoniae, and Legionella pneu-
mophila, can also play a significant role in causing Guidelines and recommendations
CAP. Selection of appropriate empiric therapy for
6,7
for treatment
RTIs therefore requires agents with activity against Primary care providers face many challenges to
a variety of gram-positive, gram-negative, and atyp- providing quality care, including a patient popu-
ical pathogens for adequate coverage. lation that lives longer but often experiences long-
Local patterns of microbial resistance must term management of complicated conditions and
also be considered. This information may be avail- multiple comorbidities. The elevated rates of an-
able from local hospital antibiograms or from timicrobial resistance can also complicate treat-
surveillance studies. The Tracking Resistance in ment decisions. To improve overall patient care,
the US Today (TRUST) program is a continu- it is necessary to identify patients with risk fac-
ous surveillance program covering 10 consecu- tors that may predict treatment failure and to
tive years of respiratory pathogens in the United optimize treatment for these patients. Current

S20 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice
Table 2

Synthesis of treatment recommendations for ABS, ABECB, and CAP

in patients with variables associated with treatment failure
ABS ABECB CAP

Low risk At risk Low risk At risk Low risk At risk

Risk Mild disease and Mild disease Mild to moderate Poor underlying Previously Presence of
no recent with recent impairment of lung function, healthy, no comorbidities
antimicrobial use antimicrobial use lung function, significant risk factors for (chronic heart,
or <4 exacerbations comorbidity drug-resistant lung, liver, or renal
mild disease per year, no (ischemic S pneumoniae disease), diabetes
and worsening significant cardiac heart disease, mellitus, alcoholism,
after 72 h on disease congestive heart malignancies,
antibiotics, or failure), asplenia, immuno-
moderate disease ≥4 exacerbations suppressant
per year, use of conditions or use
home oxygen, of immunosuppres-
chronic oral sing drugs. Use of
steroid use, antimicrobials within
antibiotic use in previous 3 months,
the past 3 months age (< 2 or >65 yr),
exposure to child in
a day-care center.

Treatment Amoxicillin, Respiratory Macrolide, Fluoroquinolone Macrolide or β-lactam plus

amoxicillin/ fluoroquinolone,* cephalosporin, or β-lactam/ doxycycline a macrolide,
clavulanate, amoxicillin/ amoxicillin, β-lactamase or doxycycline,
or cephalosporin clavulanate, doxycycline, or inhibitor or antipneumo-
(cefpodoxime, ceftriaxone, or TMP-SMX coccal fluoro-
cefuroxime, combination of quinolone‡
cefdinir), these drugs.
TMP-SMX,† Respiratory
doxycycline,† fluoroquinolone†
macrolide,† or or combination
telithromycin† of rifampicin plus
clindamycin†

ABECB, acute bacterial exacerbation of chronic bronchitis; ABS, acute bacterial rhinosinusitis; CAP, community-acquired pneumonia;
TMP-SMX, trimethoprim-sulfamethoxazole.
*The respiratory fluoroquinolones include gemifloxacin, levofloxacin, and moxifloxacin.
†
In β-lactam–allergic individuals.
‡
Fluoroquinolone with activity against S pneumoniae, including gemifloxacin, levofloxacin, and moxifloxacin.
Anon JB, et al. Otolaryngol Head Neck Surg. 2004;130(suppl 1):1-45; Balter MS, et al. Can Respir J. 2003;10(suppl B):3B-32B; Mandell LA,
et al. Clin Infect Dis. 2007;44(suppl 2):S27-S72; Niederman MS, et al. Am J Respir Crit Care Med. 2001;163:1730-1754.

management guidelines provide some direction
in identifying these at-risk patients and offer rec-
ommendations for antimicrobial selection.
Limitations of antimicrobial
guideline recommendations
The antimicrobial treatment recommendations re-
ported in this article and summarized in Tab le 2
are taken from guidelines developed by consen-
sus committees of physicians convened by pro-
fessional organizations interested in the study
and treatment of ABS, ABECB, and CAP. Where
possible, these recommendations are based on
data from randomized controlled trials, but they
also take into account information available
from smaller open trials (in ABECB and CAP). In
addition, some recommendations are based on

Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S21
Tre at m e n t fo r RT I pat i ents pr one to t reatment failur e

the bacteriologic and clinical efficacy of antibi-
otics derived from the mathematical modeling
of the disease using factors such as pathogen
distribution, resolution rates in the absence of
treatment, and in vitro microbiologic activity (in
ABS). As such, data were not always available in
a manner that allowed for the calculation of the
number needed to treat (NNT).
Acute bacterial rhinosinusitis
Antibiotic therapy for ABS seeks to eradicate exacerbation.4 Treatment with appropriate an-
bacterial pathogens from the site of infection,
helping to decrease symptom duration and allow-
ing patients to quickly resume normal daily activi-
ties.3 Eradication of bacterial pathogens returns
the sinuses to health, prevents severe complica-
tions, such as meningitis and brain abscess, and
decreases the likelihood of chronic disease.3
When a bacterial pathogen is suspected, the Si-
nus and Allergy Health Partnership Guidelines sug-
gest antimicrobial therapy based on the patient’s
history of recent antibiotic use, stratifying patients
according to antibiotic exposure within the previous
4 to 6 weeks.3 Disease severity should be assessed.3
Patients with mild disease and no recent antimi-
crobial exposure can be treated with amoxicillin require antibiotic therapy typically present with
(± clavulanate) or a cephalosporin. However, pa-
tients who have moderate disease, or those with
mild disease who have had a recent course of anti-
biotics, should be treated with a respiratory fluoro-
quinolone (levofloxacin or moxifloxacin), high-dose
amoxicillin/clavulanate, or ceftriaxone, as indicat-
ed in Tabl e 2 .3,10 Patients with complicating factors,
such as an immunodeficiency or a potential infec-
tion with penicillin-resistant S pneumoniae, can
also be treated with high-dose (4 g/day) amoxicillin tions per year, use home oxygen, take oral steroids
(± clavulanate, 250 mg/day) (Tab le 2 ).3
If the patient does not respond to the antimi-
crobial therapy after 72 hours, re-evaluation or a
switch to an alternate antimicrobial therapy is in-
dicated. The clinician should consider the cover-
age limitations of the initial agent.3 Patients who
continue to be symptomatic after appropriate
antibiotic therapy need further evaluation in addi-
tion to antibiotic therapy. A computed tomography
scan, fiber optic sinus endoscopy, or sinus aspira-
tion for culture may be necessary.3
Acute bacterial exacerbation of
chronic bronchitis
Chronic obstructive pulmonary disease (COPD) is
characterized by potentially pathogenic bacteria,
with titers that increase exponentially during an
tibiotics significantly decreases bacterial airway
burden, suggesting that appropriate antibiotic use
can reduce the symptoms of ABECB and decrease
the risk of progression to a more severe infec-
tion.1 A pivotal study by Anthonisen illustrated
that ABECB patients presenting with at least 2
of 3 symptoms (increased sputum production, in-
creased sputum purulence, and increased dyspnea)
benefited from antimicrobial therapy.11
The Canadian Thoracic Society and the Cana-
dian Infectious Disease Society developed guide-
lines using clinical features to identify high-risk
patients and guide antibiotic choices for those at
risk of treatment failure.12 Low-risk patients who
increased cough and sputum, sputum purulence,
and increased dyspnea but do not have additional
risk factors for treatment failure. These patients
may be treated with a variety of first-line agents, in-
cluding macrolides, amoxicillin, or cephalosporins
(Table 2 ).10,12 High-risk ABECB patients common-
ly present with additional risk factors, such as poor
underlying lung function (FEV1 <50% predicted)
or cardiac disease, experience 4 or more exacerba-
chronically, or have taken an antibiotic in the past
3 months. For these patients, treatment should be
directed against potential resistant organisms and
should include a respiratory fluoroquinolone or
amoxicillin/clavulanate (Table 2 ).10,12 In addition,
for those who fail initial therapy, it may be advis-
able to change the class of antibiotic.12

S22 Vol 57, No 2 / February 2008 n Supplement to The Journal of Family Practice
Community-acquired pneumonia
CAP is a common and serious illness. In patients
with severe disease who require hospitaliza-
tion, mortality rates range from 14% to 22%.7,13 or congestive heart failure (Table 2 ).14,15
S pneumoniae is the most common pathogen in
patients with CAP, followed by H influenzae and
M catarrhalis.6,13 The American Thoracic Society
and the Infectious Diseases Society of America
have developed joint guidelines for the treatment
of CAP outpatients, including management of
high-risk patients and patients with variables Treatment with an appropriate antimicrobial agent
indicative of treatment failure.6,14 A macrolide or
doxycycline is recommended for otherwise healthy
patients who lack comorbid conditions and who
have not received antibiotic therapy in the last
3 months. For patients with previous antibiotic
exposure or with potential exposure to resistant
pathogens, the guidelines recommend treatment
with a respiratory fluoroquinolone alone, for ex-
ample, levofloxacin, gemifloxacin, or moxifloxa-
cin,* or an advanced macrolide (azithromycin or
clarithromycin) plus a β-lactam such as high-dose
amoxicillin (± clavulanate), alternatives to which
include ceftriaxone, cefpodoxime, and cefuroxime
(Tab l e 2 ).6,10,14,15 Either an advanced macrolide
plus a β-lactam or a respiratory fluoroquinolone
is recommended for patients with additional risk
factors for poor outcomes, including comorbid
conditions such as COPD, diabetes, renal failure,
Conclusion
Respiratory tract infections in patients at risk of
poor outcomes are unlikely to resolve without
treatment, or to tolerate treatment failure well.
significantly decreases the bacterial burden, and
may reduce the risk of the patient progressing to
a more severe infection.1 When making treatment
choices, it is important for practitioners to consid-
er the most commonly encountered pathogens as
well as the potential for resistance to ensure that
the appropriate antimicrobial is prescribed.
Treatment guidelines from several specialty
societies provide recommendations for initial
treatment selection for the most common RTIs.
For patients with complications that increase the
probability of treatment failure, β-lactams (usu-
ally in combination with a β-lactamase inhibitor
and/or a macrolide) and respiratory fluoroquino-
lones are most commonly recommended.3,6,12,14 n

*Current guidelines do not include gatifloxacin because toxicity issues have prompted withdrawal of this agent from the market.

References
1. Adams SG, Anzueto A. Antibiotic therapy
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Semin Respir Infect. 2000;15:234-247.
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the Sinus and Allergy Health Partnership. An-
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Supplement to The Journal of Family Practice n Vol 57, No 2 / February 2008 S23
supplement to

Available at www.jfponline.com February 2008