Download Treatment of Community-Acquired Pneumonia—IDSA Guidelines*

Treatment of Community-Acquired
Pneumonia—IDSA Guidelines*
Jack M. Bernstein, MD
The Infectious Diseases Society of America (IDSA) has published guidelines for the treatment of
community-acquired pneumonia (CAP). Although Streptococcus pneumoniae remains the most
common etiologic agent, Chlamydia pneumoniae and Legionella pneumophila are also important
causes. For all suspected CAP patients, particularly those requiring hospitalization, chest
radiographs are strongly recommended to confirm the diagnosis. The IDSA guidelines, in
contrast to those published by the American Thoracic Society, emphasize the use of sputum
Gram’s stain and culture in all patients, whenever possible, to establish etiology. This information
can be used not only to guide therapy but also to track trends in the etiologic pathogens for CAP
and their antibiotic susceptibility. In light of the better outcomes with the earliest possible
interventions, the IDSA recommends initial empiric antimicrobial therapy until laboratory
results can be obtained to guide more specific therapy. Macrolides, doxycycline, and fluoroquinolones are suggested for primary empiric therapy, since each has activity against common bacterial
pathogens and atypical agents. Detailed antibiotic recommendations are made for various
pathogens. For inpatients, attempts should be made to cover Legionella and other common
pathogenic bacteria. Alternative antibiotics are recommended for patients with structural
diseases of the lung, penicillin allergy, or suspected aspiration pneumonia. Switch to an
appropriate oral antibiotic is recommended as soon as the patient’s condition is stable and he or
she can tolerate oral therapy, often within 72 h.
(CHEST 1999; 115:9S–13S)
Key words: American Thoracic Society guidelines; antibiotics; community-acquired pneumonia; empiric therapy;
etiology; Infectious Diseases Society of America guidelines
Abbreviations: ATS 5 American Thoracic Society; CAP 5 community-acquired pneumonia; IDSA 5 Infectious Diseases Society of America; SGS 5 sputum Gram’s stain
understanding of community-acquired pneuO urmonia
(CAP) has expanded greatly over the past
several years. Epidemiologic studies show that the
combined cause-of-death category of pneumonia
and influenza ranks sixth as the leading cause of
death in the United States.1 From 1979 to 1994, the
crude rate of pneumonia and influenza has increased
59%. These increases weigh heavily on the elderly,
who are more susceptible to these diseases and are
more likely to die from them. The elderly accounted
for 89% of all pneumonia and influenza deaths in
1992.2,3
Increasing death rates imply an increasing incidence within the community, but estimates are hard
to obtain because CAP is not a reportable disease to
state or federal agencies and is most often treated on
*From the Department of Veterans Affairs Medical Center and
the Department of Medicine/Veterans’ Affairs Campus, Wright
State University, Dayton, OH.
Correspondence to: Jack M. Bernstein, MD, Department of
Medicine/Veterans’ Affairs Campus, Wright State University,
PO Box 927, Dayton, OH 45435; e-mail: bernstein@wsu-id.
dayton.oh.us
an outpatient basis.4 Estimates for the incidence of
CAP are 3.5 to 4 million cases per year, with up to
20% of patients requiring hospitalization.5 Those
who enter the ICU suffer a 15 to 20% mortality rate.
Etiologic Considerations
Most CAP cases that yield an identifiable pathogen are caused by Streptococcus pneumoniae.6 Infection caused by aspiration of contents of the
oropharynx may yield a variety of organisms. Although S pneumoniae accounts for a large portion of
the pneumonias, culture reveals an expanding list of
additional causes. Haemophilus influenzae and Chlamydia pneumoniae are generally the third or fourth
most common organisms identified. Less common
etiologic agents include oral anaerobes, Staphylococcus aureus, Legionella pneumophila, Moraxella catarrhalis, and Hantavirus (Table 1). However, 30 to
60% of the CAP cases do not yield an identifiable
pathogen.7 When no pathogen is isolated, diagnosis
rests on clinical criteria, none of which are definitive.
The distribution of infective organisms varies in
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Table 1—Pathogens Typically Cultured From CAP
Pathogen
Prevalence, %
S pneumoniae
H influenzae
Oral anaerobes
S aureus
Other Gram-negative bacteria
Respiratory viruses
L pneumophila
C pneumoniae
M catarrhalis
20–60
3–10
6–10
3–5
3–10
2–15
2–8
5–17
1–3
different age groups. Figure 1 shows examples of
how the percentages of pathogens change with patient age. C pneumoniae is clearly an important
pathogen for younger patients, whereas S pneumoniae grows in significance and Mycoplasma pneumoniae decreases for the elderly. L pneumophila,
however, is most prevalent among the 35- to 49-yearold age group.
Existing Guidelines for CAP
The American Thoracic Society (ATS) and the
Canadian Infectious Disease Society have provided
guidelines to help the clinician treat CAP inpatients
and outpatients.7,8 By providing criteria to stratify
patients with the disease, these guidelines suggest
when to hospitalize the patient and what courses of
therapy may be useful. Patient stratification for
outcome focuses on the severity of the disease and
underlying risk factors for poor clinical outcome.
The ATS guidelines stress the difficulty in acquiring specific etiologic information and emphasize
instead empiric treatment of the disease. The ATS
points out that the clinical presentations of patients
infected with the same pathogen often differ. Furthermore, early chest radiographs may not show
infiltrates or other signs of inflammation, and radiographs may not provide enough information to dif-
Figure 1. Pathogens for CAP by age group.16
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ferentiate bronchitis or chronic bronchitis from
CAP.4,6 Attempts to clinch a diagnosis by culturing
an organism often fail. Indeed, a study of 154 CAP
patients using sputum culture, serologic tests, and
bronchoscopy was able to identify the pathogen only
51% of the time.9 It is this type of result that
prompted the ATS to recommend an empiric approach to CAP therapy.10
The IDSA Guidelines
The Infectious Diseases Society of America
(IDSA), which has recently reexamined the etiology
and presentations of CAP, has proposed new guidelines that may lead to more efficient care for CAP
patients.11 The guidelines seek to streamline decision making for patient care and to encourage ongoing attempts to identify the infecting organism. The
objective is to rationalize antibiotic therapy so as to
maximize the chance of cure and minimize the
likelihood of inducing pathogen resistance.
Figure 2 diagrams the recommended treatment
algorithm, emphasizing inpatient management. Entry into the algorithm begins with a patient history
consistent with CAP. This history could include such
obvious considerations as cough, fever, and previous
hospitalization for pneumonia. Additional contributing risk factors for CAP include viral infections, a
compromised immune system, neutropenia, pulmonary edema, altered consciousness, airway obstruction, and congenital pulmonary abnormalities.4
At the outset, the IDSA guidelines strongly recommend a chest radiograph for all suspected CAP
patients to confirm the presence of pneumonia.
Radiographs are particularly valuable for CAP patients admitted to the hospital, because they provide
Figure 2. Algorithm for CAP treatment. Adapted from IDSA.11
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a baseline to assess the subsequent progression or
regression of pulmonary inflammation.
Clearly, patients with more CAP risk factors are
subject to a higher risk of mortality. The IDSA
algorithm helps define which patients would benefit
from hospitalization. Clinical factors that are part of
the decision include respiratory failure, ARDS, mechanical intervention, bilateral infiltrates or a . 50%
increase in infiltrates, and a worsening chest radiograph within 48 h of hospital admission. Additional
indicators of CAP severity include systolic or diastolic hypotension, profound sepsis with end-organ
dysfunction, and tachypnea . 30 breaths/min. Although these factors can be part of patient assessment, the factors considered need not be this complex. Farr et al12 examined the prognostic power
offered by 42 different measurable clinical factors for
CAP patient outcome.12 They found that three parameters offered the clinician the best opportunity
to predict patient mortality, specifically, tachypnea
. 30 breaths/min, BUN . 19.6 mg/dL, and diastolic
BP , 60 mm Hg.
Diagnostic studies available for evaluating the
CAP patient are summarized in Table 2. Baseline
measurements include a chest radiograph, sputum
Gram’s stain (SGS), and optionally, a sputum culture
for conventional bacteria. Laboratory testing for
inpatients should include a CBC count with differential and a chemistry panel including glucose, se-
Table 2—Useful Diagnostic Studies for CAP
Evaluation11
Studies
Baseline assessment
Chest radiograph to substantiate diagnosis of pneumonia, detect
associated lung disease, provide a baseline to assess
therapeutic response, predict pathogen, and assess severity
Outpatients
SGS is desired
Culturing for conventional bacteria is optional
Inpatients
CBC count with differential
Chemistry panel, including glucose, serum sodium, liver function
tests, renal function tests, and electrolytes
HIV serologic test with informed consent for persons age 15 to
54 years in hospitals with more than one newly diagnosed
patient with HIV infection per 1,000 discharges
Blood gases
Blood cultures 3 2 (pretreatment)
Gram’s stain and culture of sputum
Test for M tuberculosis with acid-fast bacilli stain and culture in
selected patients
Test for Legionella in selected patients, including all seriously ill
patients without an alternative diagnosis, especially if . 40
years old, immunocompromised, nonresponsive to b-lactam
antibiotics, with clinical features suggesting this diagnosis, or
in outbreak setting
rum sodium, liver function, renal function, and
electrolytes. In a hospital that sees more than one
HIV-positive patient per 1,000 hospital discharges,
an HIV serologic test should be run (with permission) for patients between the ages of 15 and 54
years. Seriously ill patients who lack an alternative
diagnosis or have suggestive findings should also be
tested for Mycobacterium tuberculosis and L pneumophila.
The main difference between current ATS and
IDSA guidelines lies in a greater emphasis by the
IDSA on establishing the etiology for each case of
pneumonia. The ATS views the relatively low information return from SGS and culture as a reason to
forgo these tests. The IDSA, however, believes these
etiologic tests not only help guide treatment in
individual patients, but also provide an essential
sampling of the community’s CAP patterns. Data
from such tests allow detection of changes in the
source of infection and resistance patterns among
pathogens within the community.
These samplings are not enough, however, to
quickly detect newly emerging or resurgent infective
organisms. The “Emerging Infections Network” on
the IDSA Internet site (http://www.idsociety.org)
provides a forum for the dissemination of information about the latest trends recognized by clinicians
specializing in adult or pediatric infectious diseases.13 The Emerging Infections Network provides an
early warning system for the Centers for Disease
Control and Prevention and other public health
agencies.
The overall management goals of the IDSA guidelines pivot on the rational use of the microbiology
laboratory for both inpatient and outpatient therapy.
For outpatients, SGS is desirable, and culture for
conventional bacteria is optional. Hospitalized patients should have an SGS and culture of both
sputum and blood.11 Recommendations for therapy
are pathogen directed. Hospitalization is based on
the available prognostic criteria, and antibiotic therapy should begin as early as possible.
Approximately 80% of CAP patients will be
treated as outpatients. The IDSA guidelines call for
a pathogen-directed therapy for these individuals as
well. Diagnostic studies should include a chest radiograph and SGS. When the pathogen is unknown,
empiric therapy should include considerations of
disease severity, the patient’s age, clinical features,
comorbidity, previous antibiotic therapy, and epidemiology.
Options in Antimicrobial Therapy
Options for antimicrobial therapy are continually
evolving (Table 3). For empiric therapy, the IDSA
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Table 3—IDSA Therapeutic Alternatives for CAP11
Patient Category
Outpatients
Immunocompetent adults
With suspected penicillin-resistant S pneumoniae
With suspected aspiration
Young adults (18 to 40 years)
Hospitalized patients
General medical ward
ICU/serious pneumonia
With structural lung disease
With penicillin allergy
With suspected aspiration
Antimicrobial Recommendation
Preferred: macrolide,* fluoroquinolone,† or doxycycline
Alternatives: amoxicillin/clavulanate or second-generation cephalosporin (note: this
regimen will not be active against atypical organisms)
Fluoroquinolone†
Amoxicillin/clavulanate
Doxycycline
Preferred: b-lactam‡ with or without macrolide,* or fluoroquinolone†
Alternatives: cefuroxime with or without macrolide,* or azithromycin
b-Lactam‡ with macrolide (erythromycin or azithromycin) or fluoroquinolone†
Antipseudomonal penicillin, carbapenem, or cefepime with macrolide* or
fluoroquinolone† with aminoglycoside
Fluoroquinolone† with or without clindamycin
Fluoroquinolone† with either clindamycin or metronidazole, or penicillin/b-lactamase
inhibitor§
*Azithromycin, clarithromycin, or erythromycin.
†Levofloxacin, sparfloxacin, grepafloxacin, trovafloxacin, or other fluoroquinolone with enhanced activity against S pneumoniae.
‡Cefotaxime, ceftriaxone, or a penicillin/b-lactamase inhibitor.
§Ampicillin/sulbactam, ticarcillin/clavulanate, or piperacillin/tazobactam.
recommends macrolides, doxycycline, and fluoroquinolones as suitable alternatives for primary therapy because each has activity against common pathogens as well as many atypical organisms. In serious
cases of pneumonia (eg, in the ICU), the fluoroquinolones, erythromycin, or azithromycin should be
supplemented with cefotaxime, ceftriaxone, or a
b-lactam/b-lactamase inhibitor to provide extended
Gram-negative coverage.11
Inpatient empiric therapy for particularly severe
CAP should consider Legionella and other pathogenic bacteria as possible sources of the infection.
The therapeutic program should be modified further
for patients with structural disease of the lung,
penicillin allergy, or suspected aspiration pneumonia.
Recent studies have shown that patients can usually be switched from IV to oral therapy within 3
days, provided a good oral antibiotic is available and
that the patient is in clinically stable condition and
can tolerate the drug.14 Treatment for S pneumoniae
should generally continue for 7 to 14 days or until the
patient is afebrile for 72 h.11 Patients with atypical
pathogens should be treated for 10 to 21 days.
Azithromycin is a good choice for treatment of
atypical pathogens, but its utility against S pneumoniae depends on community susceptibility.
their conditions begin to deteriorate (Fig 3). When
this happens, one must first question whether the
initial diagnosis was correct.6 If the diagnosis was
correct, then host issues, drug issues, or pathogen
issues may be preventing a successful response. Host
issues include obstruction, foreign bodies, inadequate immune response, or superinfection. Drug
issues can include choosing the wrong drug, errors in
dosage or administration routes, or an adverse drug
reaction. Pathogen issues pivot on a correct identification of the pathogen, which may not be bacterial.
Conclusions
The recently published IDSA guidelines for the
treatment of CAP cover essentially all aspects of
When Patients Fail to Respond
The expected response to antibiotic therapy is an
amelioration of symptoms over the first 72 h. Some
patients fail to respond to initial empiric therapy or
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Figure 3. Causes for therapeutic failures.11 CHF 5 congestive
heart failure.
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patient management. They begin with a strong recommendation for chest radiographs and utilize the
hospitalization decision algorithm developed by Fine
et al.15 Diagnostic studies are strongly encouraged,
even for outpatients, to determine the etiology and
allow pathogen-specific therapy. Antibiotic recommendations for initial empiric treatment are based
on severity of illness and presence of risk factors. In
addition, specific antibiotics are recommended for a
wide range of pathogens, to assist in the switch from
relatively broad-spectrum empiric therapy to specific
therapy. Guidelines are presented to assist in the
decision of when to switch from IV to oral therapy
(often within 72 h), to determine the overall length
of therapy, and to assess patient progress. Recommendations are made for the assessment of patients
who fail to respond to initial treatment. Pneumococcal and influenza vaccines are recommended for
those at high risk for CAP (ie, . 64 years of age and
those with underlying systemic illness), consistent
with current Centers for Disease Control and Prevention guidelines. The IDSA guidelines are presented with rankings to indicate the strength of each
recommendation and the quality of the evidence
supporting that recommendation. These guidelines
are currently being integrated with the recently
revised guidelines from the ATS to create a single set
of recommendations for the treatment of CAP.
Appendix/Discussion
Dr. Bernstein: With regard to prompt initiation of therapy,
there are data that show that the longer you delay the initiation of
anti-infective therapy, the longer the hospital stay. This is the
origin of the guideline for trying to initiate therapy in the
emergency department.
Dr. Segreti: One of the problems is what you consider
“prompt” initiation of therapy. This obviously has medicolegal
connotations.
Dr. File: We actually suggested that anywhere from 2 to 8 h
was “prompt” in an early draft of the guidelines, but the data to
support the earlier number just were not there, so we took it out.
The point was we wanted to make sure that prompt initiation
occurred rather than waiting for the culture results. You should
give the antibiotics as soon as possible.
Dr. Bernstein: One quandary we face in empiric therapy is the
increasing macrolide resistance in the community. Doxycycline
still seems to be a reasonable drug, and the newer fluoroquinolones seem to be active against the majority of pathogens. I am
reluctant to prescribe macrolides since with the increasing
resistance we might start seeing failures.
Dr. File: The issue here is that you need to have good local
susceptibility data. If you use a macrolide empirically for a
hospitalized patient, and the patient ends up with a pneumococcal bacteremia, you should be able to determine macrolide
susceptibility in your laboratory if you are going to continue to
use that drug. It really depends on good microbiology, and a lot
of hospitals do not do that.
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