Treatment of Community-Acquired Pneumonia in Adults in The Outpatient Setting

21/2/24, 20:12 Treatment of community-acquired pneumonia in adults in the outpatient setting - UpToDate
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Treatment of community-acquired pneumonia in adults

in the outpatient setting
AUTHOR: Thomas M File, Jr, MD
SECTION EDITOR: Julio A Ramirez, MD, FACP
DEPUTY EDITORS: Sheila Bond, MD, Paul Dieffenbach, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.

This topic last updated: Nov 06, 2023.
INTRODUCTION
Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary

parenchyma in a patient who has acquired the infection in the community, as distinguished
from hospital-acquired (nosocomial) pneumonia (HAP).
CAP is a common and potentially serious illness [1-3]. It is associated with considerable
morbidity and mortality, particularly in older adult patients and those with major
comorbidities. (See "Morbidity and mortality associated with community-acquired
pneumonia in adults".)
The treatment of CAP in adults in the outpatient setting will be reviewed here. Other related
issues are discussed separately:
● (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in

adults".)
● (See "Community-acquired pneumonia in adults: Assessing severity and determining

the appropriate site of care".)
● (See "Treatment of community-acquired pneumonia in adults who require

hospitalization".)
● (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)
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● (See "Epidemiology, pathogenesis, and microbiology of community-acquired

● (See "Aspiration pneumonia in adults" and "Epidemiology of pulmonary infections in

immunocompromised patients".)
● (See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and
"COVID-19: Evaluation and management of adults with persistent symptoms following
acute illness ("Long COVID")" and "COVID-19: Management of adults with acute illness
in the outpatient setting".)
DEFINITIONS
CAP is defined as an acute infection of the pulmonary parenchyma in a patient who has
acquired the infection in the community, as distinguished from hospital-acquired
(nosocomial) pneumonia (HAP) ( table 1).
Health care-associated pneumonia (HCAP; no longer used) referred to pneumonia acquired

in health care facilities (eg, nursing homes, hemodialysis centers) or after recent
hospitalization [4,5]. The term HCAP was used to identify patients at risk for infection with
multidrug-resistant pathogens. However, this categorization may have been overly sensitive,
leading to increased, inappropriately broad antibiotic use and was thus retired [6-10].
Patients previously classified as having HCAP should be managed similarly to those with CAP,
with the need for therapy targeting multidrug-resistant pathogens being considered on a
case-by-case basis. Specific risk factors for resistance that should be assessed include recent
receipt of antimicrobials, major comorbidities, functional status, and severity of illness
[11,12].
INITIAL MANAGEMENT
Obtaining an accurate diagnosis, determining the treatment setting, and starting antibiotic
treatment promptly are essential early steps in CAP management.
● Establishing the diagnosis – The diagnosis of CAP generally requires the

demonstration of an infiltrate on chest imaging in a patient with a clinically compatible
syndrome (eg, fever, dyspnea, cough, and sputum production). Because clinical
features alone are nonspecific, obtaining a chest radiograph improves diagnostic
accuracy and is considered a requirement for diagnosis by the Infectious Diseases
Society of America (IDSA) and the American Thoracic Society (ATS) [10]. (See "Clinical
evaluation and diagnostic testing for community-acquired pneumonia in adults",

section on 'Chest imaging findings'.)
While the combination of a compatible clinical syndrome and imaging findings

consistent with pneumonia are sufficient to establish an initial working diagnosis of
CAP and to start empiric antibiotic therapy, this combination of findings is nonspecific
and is shared among many cardiopulmonary disorders. Thus, remaining attentive to
the possibility of an alternate diagnosis as a patient's course evolves is important to
care.
● Determining the site of care – Determining whether a patient with CAP can be safely
treated as an outpatient or requires hospital admission is an essential first step in
management, which informs downstream diagnostic and therapeutic decisions
( algorithm 1).
While severity of illness is the key determinant, other factors should also be taken into
account. These include the ability to maintain oral intake, likelihood of medication
adherence, history of active substance abuse, mental illness, cognitive or functional
impairment, and living or social circumstances (eg, homelessness, residence far
enough from a health care facility that precludes timely return to care in the event of
clinical worsening). (See "Community-acquired pneumonia in adults: Assessing severity
and determining the appropriate site of care", section on 'Approach to site of care'.)
● Microbiologic testing – For most patients with mild CAP being treated in the
ambulatory setting, microbiologic testing is not needed ( table 2) [10]. Empiric
antibiotic therapy is generally successful, and knowledge of the infecting pathogen
does not usually improve outcomes [13]. However, when clinical suspicion for a specific
pathogen is high based on clinical and/or epidemiologic features (eg, high activity of
influenza in the community, during outbreaks), microbiologic testing can be helpful,
particularly when treatment of the suspect pathogen differs from standard empiric
therapy or when there are public health implications.
Important pathogens to bear in mind when considering the need to test include
Legionella species, Mycobacterium tuberculosis, influenza A and B, avian influenza,
Middle East respiratory syndrome coronavirus, community-acquired methicillin-
resistant Staphylococcus aureus (CA-MRSA), or agents of bioterrorism. Advances in
molecular testing for etiology may allow for earlier pathogen-directed therapy than was
previously possible.
● Timing of treatment – Since patients who do not require admission are often not
given the first dose of antibiotics when they present for care, they should be counseled
to fill their prescription without delay in order to achieve the best outcome. Specific
treatment regimens are discussed below. (See 'Preferred agents' below.)
EMPIRIC ANTIBIOTIC TREATMENT
General approach — Empiric regimens are designed to cover the most common bacterial
causes of CAP encountered in the outpatient setting ( table 3).
● For all patients, our empiric regimens target Streptococcus pneumoniae, Haemophilus
influenzae, and atypical pathogens (ie, Mycoplasma pneumoniae, Legionella pneumophila,
and Chlamydia pneumoniae).
● Coverage is expanded to include or better treat certain gram-negative pathogens (eg,

beta-lactamase-producing H. influenzae, Moraxella catarrhalis, and methicillin-
susceptible S. aureus for older patients, smokers, and those with comorbidities (eg,
chronic heart, lung, liver, or kidney disease, diabetes mellitus, alcohol use disorder)
and/or recent antibiotic use.
● For patients with structural lung disease (eg, advanced chronic obstructive pulmonary
disease [COPD]), we also select a regimen that includes coverage for
Enterobacteriaceae (eg, Escherichia coli and Klebsiella spp).
The backbone of therapy is the beta-lactam, which primarily targets S. pneumoniae. Among
beta-lactams, high-dose amoxicillin and amoxicillin-clavulanate are preferred because they
remain active against most strains of S. pneumoniae, despite rising resistance rates among
macrolides, tetracyclines, and other antibiotic classes. We generally use amoxicillin-
clavulanate rather than amoxicillin in older patients, smokers, and those with comorbidities
because of its extended spectrum.
Generally, we add either a macrolide or doxycycline to the beta-lactam to target atypical

pathogens. However, the value of treating atypical pathogens in otherwise healthy patients
is debated [10,14,15]. Specifically, our approach differs from the American Thoracic
Society/Infectious Diseases Society of America (ATS/IDSA) with regard to covering atypical
pathogens in all patients ( table 4). The ATS/IDSA recommends including coverage for
atypical pathogens for all patients except outpatients who are otherwise healthy, aged <65
years old, and have not recently used antibiotics. (See 'Comorbidities, age 65 years or older,
or recent antibiotic use' below.)
Respiratory viruses (eg, influenza, parainfluenza, respiratory syncytial virus) are also among
the most frequently detected causes of CAP and may occur concurrently or independently
from bacterial infection. When influenza virus is a confirmed or suspected cause of CAP,
antiviral treatment is typically warranted. (See "Seasonal influenza in nonpregnant adults:

Treatment".)
Although a wide variety of other pathogens can cause CAP, these few described above are
responsible for the majority of cases with a known cause in the outpatient setting. Other
bacterial causes of CAP, such as MRSA, Enterobacteriaceae, and Pseudomonas aeruginosa,
tend to be associated with greater illness severity and are detected more frequently in
hospitalized patients and those with specific risk factors. (See "Treatment of community-
acquired pneumonia in adults who require hospitalization", section on 'Likely pathogens' and
"Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in
adults".)
Preferred agents — No first-line empiric antibiotic regimen has been clearly shown to be
superior to another for the empiric treatment of CAP in outpatients in clinical trials [10,16].
Thus, antibiotic selection depends on the likelihood of antibiotic resistance, patient
comorbidities, and the potential for adverse medication effects (including drug
hypersensitivity reactions) ( algorithm 2).
Specific regimens are outlined below. Modifications to these regimens may be needed based
on patient travel and exposure history, local epidemiology (eg, outbreaks, family clusters), or
when specific pathogens are suspected (eg, influenza viruses, CA-MRSA, M. tuberculosis). The
doses given below are intended for patients with normal renal and hepatic function; the
doses of certain agents should be reduced in patients with organ dysfunction.
Healthy, age <65 years, no recent antibiotic use — For otherwise healthy patients aged
<65 years who have not recently used antibiotics, we typically use an empiric regimen that
targets S. pneumoniae, H. influenzae, and atypical pathogens (ie, M. pneumoniae, L.
pneumophila, and C. pneumoniae) ( algorithm 2).
● For most patients in this category, we treat with high-dose amoxicillin (1 g orally three
times daily) plus either a macrolide (ie, azithromycin, clarithromycin) or doxycycline.
Macrolides are generally preferred over doxycycline, unless there are contraindications.
(See 'Caveats for fluoroquinolones and macrolides' below.)
● For patients with mild non-immunoglobulin (Ig)E-mediated reactions to penicillin (eg

maculopapular rash) or known tolerance to cephalosporins, a third-generation
cephalosporin (eg, cefpodoxime) is the preferred alternative to amoxicillin. Like
amoxicillin, we give the cephalosporin in combination with an agent that targets
atypical pathogens. For patients with IgE-mediated reactions (eg, urticaria,
angioedema, anaphylaxis) or severe delayed reactions, empiric use of cephalosporins
should generally be avoided. (See "Penicillin allergy: Immediate reactions" and
"Penicillin allergy: Delayed hypersensitivity reactions".)
● When the above regimens cannot be used, we generally treat with a respiratory
fluoroquinolone (ie, levofloxacin, moxifloxacin, gemifloxacin). We have begun to adopt
lefamulin monotherapy into practice, particularly for patients who cannot tolerate beta-
lactams and wish to avoid the potential adverse effects associated with
fluoroquinolones [17,18]. However, clinical experience with lefamulin is limited and use
may be limited by cost and/or availability. Lefamulin has a more targeted spectrum for
standard CAP patients than the fluoroquinolones but does not cover
Enterobacteriaceae. Use should be avoided in patients with moderate to severe hepatic
dysfunction, known long QT syndrome, or in those taking QT-prolonging agents,
pregnant and breastfeeding women, and women with reproductive potential not using
contraception. There are drug interactions with CYP3A4 and P-gp inducers and
substrates; in addition, lefamulin tablets are contraindicated with QT-prolonging
CYP3A4 substrates. Refer to the drug interactions program included within UpToDate.
(See "Treatment of community-acquired pneumonia in adults who require
hospitalization", section on 'New antimicrobial agents'.)
ATS/IDSA guidelines — Our overall approach to empiric therapy for patients with CAP is
similar to that outlined in the 2019 American Thoracic Society (ATS)/Infectious Diseases
Society of America (IDSA) guidelines [10]. However, we differ in our treatment approach for
outpatients who lack comorbidities or risk factors for drug resistance ( table 4). The
ATS/IDSA guidelines recommend monotherapy with amoxicillin as first-line treatment;
monotherapy with either doxycycline or a macrolide (if local macrolide-resistant S.
pneumoniae rates are <25 percent) are suggested alternates. Amoxicillin is preferred over
other agents because S. pneumoniae is the primary relevant bacterial pathogen in this
setting, and rates of resistance to doxycycline and macrolides among S. pneumoniae are
growing. For macrolides, resistance rates among S. pneumoniae are often >30 percent in the
United States and typically >25 percent for most parts of the world, apart from some regions
in Northern Europe. For doxycycline, resistance rates are less well established but are
approximately 10 to 20 percent in the United States and likely rising. Although atypical
pathogens are less prominent causes of CAP, they have accounted for 22 percent of cases in
some studies [18]. (See "Resistance of Streptococcus pneumoniae to the macrolides, azalides,
and lincosamides" and "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics"
and "Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and
trimethoprim-sulfamethoxazole".)
We agree with the preference for amoxicillin over other agents but prefer to add an agent
that also targets atypical pathogens because there is a potential morbidity benefit and the
downside of a short course of therapy for most patients is low. Unfortunately, there are little
data to inform outpatient practice in this regard. Trials performed in hospitalized patients
with CAP suggest that the addition of atypical coverage improves time to clinical stability and
decreases clinical failure rates, particularly among patients ultimately diagnosed with
pneumonia due to an atypical pathogen and those with more severe pneumonia [19-21].
Because pneumonia caused by atypical pathogens can be severe and cannot be clearly
distinguished from other types of pneumonia at the time of diagnosis, we generally favor
empiric treatment with a regimen that includes treatment for atypical pathogens for all
outpatients as well. (See "Treatment of community-acquired pneumonia in adults who
require hospitalization", section on 'Atypical bacteria'.)
Comorbidities, age 65 years or older, or recent antibiotic use — For patients with major
comorbidities (ie, chronic pulmonary, liver, heart, or renal disease, cancer, diabetes,
congestive heart failure, alcohol dependence, immunosuppression), smokers, or those who
have used antibiotics within the prior three months, we expand coverage to better treat
beta-lactamase-producing H. influenzae, M. catarrhalis, and methicillin-susceptible S. aureus in
addition to S. pneumoniae and atypical pathogens. For those with structural lung disease, we
further expand coverage to treat Enterobacteriaceae (eg, E. coli, Klebsiella spp)
( algorithm 2) [10,22].
● For most patients in this category, we treat with amoxicillin-clavulanate (875 mg orally
twice daily or the extended-release formulation dose at 2 g orally twice daily) plus a
macrolide (ie, azithromycin, clarithromycin) or doxycycline. In general, we prefer
macrolides over doxycycline because their use has been associated with improved
outcomes in patients with more severe CAP (possibly due to their immunomodulatory
effect) [23-26]. However, for patients who have contraindications to macrolides (eg, risk
for or known prolonged QTc, allergy), doxycycline is an appropriate alternative. (See
'Caveats for fluoroquinolones and macrolides' below.)
● When amoxicillin-clavulanate cannot be used (eg, due to allergy or other intolerance), a

third-generation cephalosporin, such as cefpodoxime, is our preferred alternative. As
with amoxicillin-clavulanate, cephalosporins should be given in combination with either
a macrolide or doxycycline. In general, patients with mild non-IgE-mediated reactions
(eg, maculopapular rash) to penicillin can generally use third-generation
cephalosporins safely. Patients with IgE-mediated reactions (hives, angioedema,
anaphylaxis) or severe delayed reactions should generally use other agents. (See
"Penicillin allergy: Immediate reactions" and "Penicillin allergy: Delayed hypersensitivity
reactions".)
● Despite its greater convenience, we reserve monotherapy with respiratory

fluoroquinolone (levofloxacin, moxifloxacin, gemifloxacin) for patients who cannot
tolerate either of the above regimens (eg, due to IgE-mediated or severe, delayed
hypersensitivity reactions to penicillin) because of its adverse effect profile and the
potential of promoting fluoroquinolone resistance. (See 'Caveats for fluoroquinolones
and macrolides' below.)
● We have also begun to adopt lefamulin monotherapy into practice, particularly for
patients without structural lung disease (eg, advanced COPD) who cannot tolerate beta-
lactams and wish to avoid the potential adverse effects associated with
fluoroquinolones [17,18]. However, clinical experience with lefamulin is limited, use may
be limited by cost and/or availability, and it does not cover Enterobacteriaceae. Use
should be avoided in patients with moderate to severe hepatic dysfunction, known long
QT syndrome, or in those taking QT-prolonging agents, pregnant and breastfeeding
women, and women with reproductive potential not using contraception. There are
drug interactions with CYP3A4 and P-gp inducers and substrates; in addition, lefamulin
tablets are contraindicated with QT-prolonging CYP3A4 substrates. Refer to the drug
interactions program included within UpToDate.
● Omadacycline is another newer agent that is active against most CAP pathogens,
including Enterobacteriaceae. It is a potential alternative for patients who cannot
tolerate beta-lactams (or other agents) and want to avoid fluoroquinolones. Studies
that support its use have been performed in hospitalized patients. (See "Treatment of
community-acquired pneumonia in adults who require hospitalization", section on 'New
antimicrobial agents'.)
ATS/IDSA guidelines — Our overall approach to empiric therapy for patients with CAP is
similar to that outlined in the 2019 American Thoracic Society/Infectious Diseases Society of
America (ATS/IDSA) guidelines [10]. However, we prefer to use an amoxicillin-clavulanate-
based regimen because amoxicillin-clavulanate has reliable activity against S. pneumoniae
and an overall favorable adverse effect profile. By contrast, the ATS/IDSA guidelines do not
state a preference among beta-lactams nor between beta-lactam-based regimens and
fluoroquinolone monotherapy ( table 4). In a systematic review of 11 randomized trials
evaluating >3300 adults and adolescents with CAP treated in the outpatient setting, clinical
cure rates were similar when comparing various treatment regimens, including macrolides,
fluoroquinolones, and beta-lactams [16]. However, most included trials were small and many
evaluated medications that are no longer available. Data from the inpatient setting are more
robust and suggest that the overall efficacy of combination beta-lactam-macrolide therapy
and fluoroquinolone monotherapy is similar [27-29]. (See "Treatment of community-acquired
pneumonia in adults who require hospitalization".)
Caveats for fluoroquinolones and macrolides — Although fluoroquinolones are frequently

used for treatment of CAP, their use is discouraged in ambulatory patients with CAP without
comorbid conditions or recent antimicrobial use unless use of other regimens is not feasible.
There is concern that widespread use of fluoroquinolones in outpatients will promote the
development of fluoroquinolone resistance among respiratory pathogens (as well as other
colonizing pathogens) and may lead to an increased incidence of Clostridioides difficile colitis
[30]. In addition, empiric use of fluoroquinolones should not be used for patients at risk for
M. tuberculosis without an appropriate assessment for tuberculosis infection. The
administration of a fluoroquinolone in patients with tuberculosis has been associated with a
delay in diagnosis, increase in resistance, and poor outcomes. Despite these caveats about
fluoroquinolones, they continue to be given, often inappropriately, for CAP [13]. (See
"Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology",
section on 'Antibiotic use'.)
Macrolides, lefamulin, and fluoroquinolones can cause a prolonged QT interval, which can
result in torsades de pointes. Studies assessing the risk-benefit ratio of azithromycin are
reviewed elsewhere (see "Azithromycin and clarithromycin", section on 'QT interval
prolongation and cardiovascular events'). For outpatients with known QT interval
prolongation and for those considered to be at high risk of QT interval prolongation, we
favor doxycycline since it is not associated with QT interval prolongation. However,
doxycycline should be avoided during pregnancy. It should also be noted that doxycycline
has been less well studied for the treatment of CAP than the macrolides or fluoroquinolones.
Risk factors for QT interval prolongation include advanced age, hypokalemia,
hypomagnesemia, clinically significant bradycardia, and the use of other agents that prolong
the QT interval, including class IA (quinidine, procainamide) and class III (dofetilide,
amiodarone, sotalol) antiarrhythmic agents and certain azoles (eg, voriconazole,
posaconazole). (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes"
and "Pharmacology of azoles", section on 'Selected clinical effects' and "Azithromycin and
clarithromycin", section on 'QT interval prolongation and cardiovascular events' and
"Fluoroquinolones", section on 'QT interval prolongation'.)
PATHOGEN-DIRECTED THERAPY
Pathogen-directed therapy is less common in the outpatients setting because microbiologic

testing is typically not preformed (apart from coronavirus disease 2019 [COVID-19] testing
during the pandemic). However, as molecular diagnostics become increasingly available and
both cost and turnaround time decrease, microbiologic diagnoses are being more frequently
made in ambulatory patients. (See "Clinical evaluation and diagnostic testing for community-
acquired pneumonia in adults", section on 'Microbiologic testing'.)
● Bacterial CAP – If a bacterial cause of CAP has been identified using reliable
microbiologic methods, antimicrobial therapy should be directed at that pathogen
( table 5). Directed therapy for selected bacterial pathogens is discussed separately.
(See "Pneumococcal pneumonia in patients requiring hospitalization" and "Mycoplasma
pneumoniae infection in adults" and "Pneumonia caused by Chlamydia pneumoniae in
adults" and "Treatment and prevention of Legionella infection" and "Pseudomonas

aeruginosa pneumonia".)
● Viral CAP – Deciding whether to stop empiric antibiotic therapy for outpatients when a
virus has been detected on testing is challenging. The approach varies among experts
and is generally based on the specific virus detected, the certainty that the virus is the
sole pathogen, and patient characteristics (eg, severity of illness, risk factors for poor
outcomes, ability to follow-up closely).
For patients who are diagnosed with a virus that is known to cause pneumonia (eg,
influenza), who do not have chest imaging findings that suggest bacterial
superinfection (eg, lobar consolidation or alveolar consolidation), and at least one other
objective factor that indicates a bacterial infection is unlikely (eg, procalcitonin <0.25
ng/dL, negative sputum cultures, negative respiratory pathogen panel [ie, multiplex
polymerase chain reaction testing for bacterial and respiratory pathogens]), it is
reasonable to withhold antibiotics provided that close follow-up can be arranged. A
normal white blood cell count also makes the diagnosis of bacterial pneumonia less
likely, though this is nonspecific. When resources for testing are not available or when it
is uncertain whether the virus is the sole pathogen, we continue antibiotics because
bacterial coinfection carries the risk of substantial morbidity.
● COVID-19 – Patients with COVID-19 and pneumonia should generally be hospitalized

and treated with COVID-19 specific therapy, especially those who need supplemental
oxygen (eg, remdesivir, glucocorticoids). Because bacterial superinfection appears to be
less common in patients with COVID-19 than with other viruses, our threshold to
initiate antibiotic therapy or stop it early is lower than with other viral infections. This is
discussed in detail separately. (See "COVID-19: Management in hospitalized adults",
section on 'Empiric treatment for bacterial pneumonia in selected patients'.)
LIMITED ROLE FOR GLUCOCORTICOIDS
We do not use glucocorticoids for the treatment of CAP in the outpatient setting because the
potential harms likely outweigh any potential benefit. The benefit-to-risk ratio for
glucocorticoid use appears to be greatest in critically ill patients with CAP and we do use
glucocorticoids for selected critically ill patients. (See "Treatment of community-acquired
pneumonia in adults who require hospitalization", section on 'Adjunctive glucocorticoids'.)
Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) commonly co-occur

with CAP. For outpatients with AECOPD and CAP, we treat with either inhaled or oral
glucocorticoids depending on the severity of the AECOPD. In these circumstances, the use of
glucocorticoids is for the treatment of AECOPD, not for the treatment of CAP. (See "COPD
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exacerbations: Management", section on 'Home or office management of COPD

exacerbations'.)
DURATION OF THERAPY
We treat most ambulatory patients with CAP for five days. Because of its long half-life,
receiving azithromycin at a dose of 500 mg daily can usually be treated for three days.
Patients should be afebrile for ≥48 hours and clinically stable before therapy is discontinued.
When this is achieved, the persistence of other symptoms (eg, dyspnea, cough) is not an
indication to extend the course of antibiotic therapy.
Several meta-analyses evaluating patients with mild to moderate CAP found comparable
clinical outcomes with less than seven days compared with more than seven days of
antimicrobial therapy [31-33]. In one meta-analysis of 21 trials evaluating 4861 patients with
CAP, no significant difference in clinical cure or relapse rates were detected when comparing
antibiotic durations of ≤6 days versus durations of ≥7 days [33]. Mortality and serious
adverse event rates were lower among those treated with shorter courses (risk ratio [RR]
0.52, 95% CI 0.33-0.82, and RR 0.73, 95% CI 0.55-0.97, respectively). Trials included in this
analysis compared antibiotics from different classes and/or antibiotics with different half-
lives, which may confound results. However, in a previous meta-analysis of five randomized
trials evaluating adults with CAP comparing short (3 to 7 days) versus long (7 to 10 days)
antibiotic courses, no differences in clinical success, relapse, or mortality were detected [32].
Most trials included in these meta-analyses evaluated hospitalized patients. Direct evidence
supporting the optimal duration of therapy for outpatients with CAP is lacking [34].
FOLLOW-UP CARE
Assessing clinical response — All patients who are treated for CAP at home should have a
follow-up visit or communication with a health care provider within 24 to 48 hours after
being diagnosed to determine whether they are feeling better and to assess whether any
complications of pneumonia have developed. Patients who have not responded to therapy
after 48 to 72 hours should be re-evaluated. In addition, a later visit (eg, in one to four
weeks) is often appropriate to ensure that symptoms continue to resolve and comorbid
conditions (eg, heart failure, chronic obstructive pulmonary disease) have not worsened or
newly developed.
Most patients with CAP begin to improve soon after the initiation of appropriate antibiotic
therapy as evidenced by resolution of symptoms, physical findings, and laboratory signs of
active infection. However, some symptoms persist as the patient convalesces ( table 6) [35-
37]. This was illustrated in a study of sequential interviews in 134 ambulatory patients with
CAP [35]. The median time to resolution ranged from 3 days for fever to 14 days for both
cough and fatigue. At least one symptom (eg, cough, fatigue, dyspnea) was still present at 28
days in one-third of patients. In another report, 76 percent had at least one symptom at 30
days, most commonly fatigue, compared with 45 percent by history in the one month prior
to the onset of CAP [37]. These symptoms are usually not sufficient to interfere with work, as
illustrated in a review of 399 ambulatory patients with CAP in which the median time of
return to work was 6 days even though one-third had at least one persistent symptom at 14
days [36]. (See "Morbidity and mortality associated with community-acquired pneumonia in
adults", section on 'Short-term morbidity and mortality'.)
Chest radiograph — We do not routinely obtain a follow-up chest radiograph in patients

with CAP who have responded to therapy, as radiographic findings tend to lag behind clinical
response [10,38-41]. This approach is similar to that outlined by the American Thoracic
Society (ATS)/Infectious Diseases Society of America (IDSA), which recommends not obtaining
a follow-up chest radiograph in patients whose symptoms have resolved within five to seven
days [10].
Nonresolving CAP — In a small minority of patients treated in the outpatient setting, initial
symptoms will neither progress nor improve following empiric antibiotic treatment. We
generally characterize these patients as having nonresolving pneumonia. Potential causes of
nonresolving CAP include:
● Delayed clinical response – For some patients, particularly those with multiple
comorbidities, more severe pneumonia, and infection with certain pathogens (eg, S.
pneumoniae), treatment response may be slow.
● Loculated infection – Patients with complications such as lung abscess, empyema, or

other closed-space infections may fail to improve clinically despite appropriate
antibiotic selection. Such infections may require drainage and/or prolonged antibiotic
treatment. (See "Lung abscess in adults" and "Epidemiology, clinical presentation, and
diagnostic evaluation of parapneumonic effusion and empyema in adults".)
● Bronchial obstruction – Bronchial obstruction (eg, by a tumor) can cause a

postobstructive pneumonia that may fail to respond or may slowly respond to standard
empiric antibiotic regimens for CAP.
● Pathogens that cause subacute/chronic CAP – M. tuberculosis, nontuberculous

mycobacteria (eg, Mycobacterium kansasii), fungi (eg, Histoplasma capsulatum,
Blastomyces dermatitidis), or less common bacteria (eg, Nocardia spp, Actinomyces
israelii) can cause subacute or chronic pneumonia that may fail to respond or may
incompletely respond to standard empiric antibiotic regimens for CAP.
● Incorrect initial diagnosis – Failure to improve also raises the possibility of an

alternate diagnosis (eg, malignancy or inflammatory lung disease). (See "Overview of
community-acquired pneumonia in adults", section on 'Differential diagnosis'.)
Once a patient is characterized as having nonresolving CAP, a complete, new physical

examination, laboratory evaluation, imaging studies, and microbiologic workup will be
necessary to define the etiology of nonresolving CAP [42]. Initiation of workup for
nonresolving CAP should not be automatically associated with a change in initial empiric
antibiotic therapy. (See "Nonresolving pneumonia".)
PREVENTION
Pneumococcal and influenza vaccination — Vaccination is an effective and important

component of pneumonia prevention.
● Annual vaccination against seasonal influenza viruses is indicated for all patients
(without contraindications). (See "Seasonal influenza vaccination in adults".)
● Pneumococcal vaccination is indicated for all patients ≥65 years old and others with
specific risk factors (eg, certain comorbidities including chronic heart, lung, and liver
disease, immunocompromising conditions, and impaired splenic function). (See
"Seasonal influenza vaccination in adults" and "Pneumococcal vaccination in adults".)
Recommendations for other routine vaccinations are provided separately. (See "Standard
immunizations for nonpregnant adults".)
Smoking cessation — Smoking cessation should be a goal for patients with CAP who
smoke, and we discuss this at the time of diagnosis and when providing follow-up care. (See
"Overview of smoking cessation management in adults".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Community-acquired
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
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and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles on
a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Pneumonia in adults (The Basics)")
● Beyond the Basics topic (see "Patient education: Pneumonia in adults (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
● Epidemiology – Community-acquired pneumonia (CAP) is one of the most common

conditions encountered in the outpatient setting and can be associated with significant
morbidity, particularly for older patients, smokers, and those with comorbidities and
immunosuppression. (See 'Introduction' above.)
● Principles of antibiotic selection – For all outpatients, our empiric regimens are
designed to treat the most common bacterial causes of CAP, which include
Streptococcus pneumoniae, Haemophilus influenzae, and atypical pathogens (ie,
Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae)
( table 3). Coverage is expanded to better treat additional gram-negative pathogens
(eg, beta-lactamase-producing H. influenzae, Moraxella catarrhalis) for those with
comorbidities, older age, or recent antibiotic use. For patients with structural lung
disease (eg, advanced chronic obstructive pulmonary disease), we also select a regimen
that includes coverage for Enterobacteriaceae (eg, Escherichia coli and Klebsiella spp).
(See 'Empiric antibiotic treatment' above.)
● The importance of S. pneumoniae – The backbone of therapy is the beta-lactam, which

primarily targets S. pneumoniae (the most common and virulent bacterial CAP
pathogen). Among beta-lactams, high-dose amoxicillin and amoxicillin-clavulanate are
preferred because they remain active against most strains of S. pneumoniae, while
resistance rates among many other drug classes are rising. A macrolide or doxycycline
is added to the beta-lactam to target atypical pathogens. (See 'General approach'
above.)
● Our approach to empiric antibiotic selection – Selection of a specific regimen

depends on patient age, comorbidities (ie, chronic pulmonary, liver, heart, or kidney
disease; cancer, diabetes mellitus, heart failure, alcohol use disorder), smoking status,
and antibiotic use within the prior three months ( algorithm 2).
Modifications to these regimens may be needed based on patient travel and exposure
history, local epidemiology (eg, outbreaks, family clusters), or when specific pathogens
are suspected (eg, influenza viruses, community-acquired methicillin-resistant
Staphylococcus aureus, Mycobacterium tuberculosis). (See 'General approach' above.)
Our approach is generally similar to the American Thoracic Society/Infectious Diseases

Society of America (ATS/IDSA) guidelines with few exceptions ( table 4).
• For otherwise healthy outpatients aged <65 years who have not used
antibiotics within the prior three months, we suggest combination high-dose
amoxicillin (1 g orally three times daily) plus either a macrolide or doxycycline rather
than monotherapy with any of these agents (Grade 2C). While the value of adding
treatment for atypical pathogens is debated for this population, there is a potential
morbidity benefit and the downside of a short course of therapy for most patients is
low. (See 'Healthy, age <65 years, no recent antibiotic use' above.)
• For outpatients aged ≥65 years, smokers, and patients with comorbidities
and/or recent antibiotic use, we suggest amoxicillin-clavulanate (875 mg orally
twice daily or the extended-release formulation at 2 g orally twice daily) plus either a
macrolide or doxycycline over other regimens (Grade 2C). We prefer the amoxicillin-
clavulanate-based regimens over other regimens for its greater activity against S.
pneumoniae and its favorable adverse effect profile. (See 'Comorbidities, age 65
years or older, or recent antibiotic use' above.)
● Penicillin allergy – For patients who cannot use penicillins, combination therapy with a
third-generation cephalosporin (eg, cefpodoxime) plus a macrolide or doxycycline is our
preferred alternative. In general, patients with mild non-immunoglobulin E-mediated
reactions (eg, maculopapular rash) to penicillin, and those known to tolerate
cephalosporins, can generally safely use later-generation cephalosporins ( table 7).
Patients with more severe penicillin hypersensitivity reactions should generally avoid
empiric treatment with beta-lactams. (See 'Preferred agents' above.)
● Fluoroquinolones and other alternative agents – Fluoroquinolone monotherapy is

equally effective as our preferred regimens; however, because of its adverse effect
profile and potential for promoting drug resistance, we reserve fluoroquinolone use for
patients who cannot tolerate these regimens. Lefamulin and omadacycline are newer
agents and potential alternatives for selected patients who cannot tolerate beta-
lactams (or other agents) and want to avoid the adverse effects associated with
fluoroquinolones. However, clinical experience with these agents is limited, and there
are contraindications to their use. (See 'Preferred agents' above and 'Caveats for
fluoroquinolones and macrolides' above.)
● Duration of therapy – A five-day course of antibiotic therapy is sufficient for most

patients. In general, a follow-up visit or communication is indicated within a few days of
starting treatment to ensure that the patient is improving. Although some symptoms
may persist ( table 6), patients who have not clinically responded to treatment after
48 to 72 hours should be re-evaluated. (See 'Duration of therapy' above and 'Follow-up
care' above.)
ACKNOWLEDGMENT
UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed on

earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious
Diseases.
Use of UpToDate is subject to the Terms of Use.
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Topic 7031 Version 75.0
GRAPHICS
Pneumonia terminology
Term Definition
Classification by site of acquisition
Community-acquired An acute infection of the pulmonary parenchyma acquired outside of

pneumonia (CAP) health care settings
Nosocomial pneumonia An acute infection of the pulmonary parenchyma acquired in hospital

settings, which encompasses hospital-acquired pneumonia and
ventilator-associated pneumonia
Hospital-acquired Pneumonia acquired ≥48 hours after hospital admission; includes both
pneumonia (HAP) HAP and VAP
Ventilator-associated Pneumonia acquired ≥48 hours after endotracheal intubation

pneumonia (VAP)
Health care-associated Retired term, which referred to pneumonia acquired in health care
pneumonia (HCAP) facilities (eg, nursing homes, hemodialysis centers) or after recent
hospitalization*
Classification by etiology
Atypical pneumonia Pneumonia caused by "atypical" ¶ bacterial pathogens including

Legionella spp, Mycoplasma pneumoniae, Chlamydia pneumoniae,
Chlamydia psittaci, and Coxiella burnetii
Aspiration pneumonia Pneumonia resulting from entry of gastric or oropharyngeal fluid,

which may contain bacteria and/or be of low pH, or exogenous
substances (eg, ingested food particles or liquids, mineral oil, salt or
fresh water) into the lower airways
Chemical pneumonitis Aspiration of substances (eg, acidic gastric fluid) that cause an
inflammatory reaction in the lower airways, independent of bacterial
infection
Bacterial aspiration An active infection caused by inoculation of large amounts of bacteria

pneumonia into the lungs via orogastric contents
* The term HCAP was used to identify patients at risk for infection with multidrug-resistant
pathogens. This categorization may have been overly sensitive, leading to increased, inappropriately
broad antibiotic use.
¶ The origin of the term "atypical" is a matter of debate. The term may refer to the fact that these
organisms are not "typical" bacteria, which cannot be identified by standard microbiologic techniques.
Others suggest that atypical refers to the mild nature of the pneumonia caused by some of these
organisms compared with pneumonia caused by Streptococcus pneumoniae.
Graphic 130821 Version 3.0
Community-acquired pneumonia: Determining the appropriate site of

treatment in adults
ICU: intensive care unit; ED: emergency department; PSI: Pneumonia Severity Index; PaO2: partial
pressure of oxygen; FiO2: fraction of inspired oxygen; CURB-65: confusion, uremia, respiratory rate,
blood pressure, age ≥65 years; CAP: community-acquired pneumonia.
* Among the available scoring systems for determining the need for admission in patients with CAP,
we prefer the PSI because it is the best studied and validated. If a less complex scoring system is
desired, the CURB-65 score is a reasonable alternative, although its effectiveness and safety in
guiding the initial site of treatment have not been empirically assessed. Refer to the UpToDate topic
on assessing severity and determining the appropriate site of care in patients with CAP for additional
details and to access PSI and CURB-65 calculators.
¶ Scoring systems, such as the PSI and CURB-65, and clinical criteria are intended to supplement
rather than override the judgment of the physician. Factors other than the predictors included in the
rules and the clinical criteria may be important when making an admission decision or selecting the
site of inpatient care. As examples, patients with early signs of sepsis or rapidly progressive illness are
not well represented by severity scores. Patients with these features may warrant hospitalization
and/or ICU admission regardless of score. Conversely, older age may be overrepresented in severity
scores; this should be taken into account when determining site of care.
Δ Using the CURB-65 score, if the patient has a score of 1 because he or she is ≥65 years of age and
he or she has no major comorbidities, hospital admission is not necessarily indicated.
◊ Although a definitive etiologic diagnosis is often not established until after the site of treatment
decision has been made, clinical or epidemiologic evidence favoring pathogens associated with
rapidly progressive forms of pneumonia (eg, postinfluenza bacterial pneumonias, severe acute
respiratory syndrome, Middle East respiratory syndrome, avian influenza [eg, H5N1, H7N9], Legionella
pneumonia, coronavirus disease 2019) indicate a need to perform close clinical follow-up to monitor
severity of illness particularly for patients initially deemed low risk at presentation and treated outside
of the hospital setting.
§ Some PSI class II and III patients may benefit from in-home health care support, also termed
"hospital-at-home" (eg, a visiting nurse, intravenous fluids, intravenous antibiotics).
¥ Depending on clinical judgement, such patients may also be managed as outpatients with in-home
health care support (eg, visiting nurse, intravenous fluids, intravenous antibiotics), or with a brief (<23
hour) observational stay.
Community-acquired pneumonia: Initial evaluation and site of care based on

severity assessment in adults
Microbiologic
Severity score* Site of care
evaluation
Mild PSI: I or II Ambulatory care COVID-19 testing

or during the pandemic
Influenza testing
CURB-65: 0 ¶
(when incidence is
high and results
would change
management) Δ
Otherwise, testing is
usually not needed
Moderate PSI: III or IV General medical ward Blood cultures

or Sputum Gram stain
and culture
CURB-65: 1 ¶ to 2
Urine streptococcal
antigen
Legionella testing ◊
Respiratory viral pane
during respiratory
virus season §
COVID-19 testing ¥
HIV screening ‡
Severe PSI: IV or V ICU Blood cultures

or Sputum Gram stain
and culture
CURB-65: ≥3
Urine streptococcal
and/or antigen test
Fulfillment of ATS/IDSA Legionella testing ◊
criteria for ICU Respiratory viral
admission † panel §
Bronchoscopy
specimens for Gram
stain, fungal stain,
aerobic, fungal
culture, and
molecular testing
(when feasible)**
COVID-19 testing ¥
HIV screening ‡
CAP presents along a continuum of severity. For practical purposes, we typically categorize CAP as
mild, moderate, or severe. Severity assessment is based on clinical judgement and can be aided by
severity scores, such as the PSI or the CURB-65 score. We generally prefer the PSI as it is better
validated; however, many clinicians prefer the CURB-65 as it is easier to use. The three levels of
severity correspond to the three levels of care (ambulatory care, hospital admission to the general
medical ward, and ICU). The severity assessment and site of care each inform the initial microbiologic
evaluation and empiric antibiotic selection. For all patients, we modify our approach based on patient-
specific factors such as epidemiologic exposures and ability to care for oneself at home. Refer to the
UpToDate topic on the treatment of CAP for further detail.
PSI: Pneumonia Severity Index; COVID-19: coronavirus disease 2019; ATS: American Thoracic Society;
IDSA: Infectious Diseases Society of America; ICU: intensive care unit; CAP: community-acquired
pneumonia; PCR: polymerase chain reaction; PaO2/FiO2: arterial oxygen tension to fraction of inspired
oxygen.
* Severity scores should be used as an adjunct to clinical judgment. Patients with early signs of sepsis
(eg, patients fulfilling minor ATS/IDSA criteria) or rapidly progressive illness are not well represented
in severity scoring systems. Patients with these features may warrant hospitalization and/or ICU
admission regardless of score. Conversely, older age may be overrepresented in severity scores; this
should be taken into account when determining site of care.
¶ Because age >65 years is a criterion in the CURB-65 score, patients with CURB-65 scores of 1 who
are older than 65 years may also be reasonably treated in the ambulatory setting.
Δ Refer to the UpToDate content on the diagnosis of influenza for detail.
◊ PCR on sputum sample is preferred for the diagnosis of Legionella spp because it detects most
clinically relevant Legionella spp. The urine antigen test is an acceptable alternative when PCR is not
available but is specific for Legionella pneumophila serogroup 1.
§ The approach to testing for respiratory viruses varies among institutions. At a minimum, testing for
influenza by PCR should be performed. However, testing is often expanded to include adenovirus,
parainfluenza, respiratory syncytial virus, and human metapneumovirus. The specific assay used (eg,
PCR, serology, culture) may also vary among institutions. Results from multiplex PCR assays should be
interpreted with caution because most multiplex PCR assays have not been approved for use on lower
respiratory tract specimens.
¥ Testing for COVID-19 is recommended for all patients during the pandemic. Refer to the related
UpToDate content on the approach to testing.
‡ Refer to UpToDate content on screening and diagnosis of HIV infection for detail.
† ATS and IDSA major criteria for ICU admission include either septic shock with need for vasopressor
support and/or respiratory failure with need for mechanical ventilation. If major criteria are not met,
patients should also be considered for ICU admission if 3 or more of the following minor criteria are
present: altered mental status, hypotension requiring fluid support, temperature <36°C/96.8°F,
respiratory rate ≥30 breaths/minute, PaO2/FiO2 ratio ≤250, blood urea nitrogen ≥20 mg/dL (7
mmol/L), leukocyte count <4000 cells/microL, platelet count <100,000/mL, or multilobar infiltrates.
** We generally weigh the benefits of obtaining a microbiologic diagnosis against the risks of the
bronchoscopy (eg, need for intubation, bleeding, bronchospasm, pneumothorax) on a case-by-case
basis. When pursuing bronchoscopy, we usually send specimens for aerobic and anaerobic culture,
Legionella culture, fungal stain and culture, and testing for viral pathogens (influenza, adenovirus,
parainfluenza, respiratory syncytial virus, and human metapneumovirus).
Microbial etiology of community-acquired pneumonia by site of care*
Outpatients Ward patients In
United
Spain [1 ] Canada [2] Spain [1]
States [3]
Total patients 514 507 2521 585 488

evaluated
Patients in whom 161 (31.3) 244 (48.1) 1042 (41) 120 (21) 260
a pathogen was
identified
Patients in whom 353 (68.7) 263 (51.9) 1479 (59) 465 (79) 228
no pathogen was
identified
Pathogen ¶
Streptococcus 56 (10.9) 30 (5.9) 447 (17.7) 38 (6.5) 110

pneumoniae
Other 0 5 (1.0) 0 0 0
Streptococcus
spp
Haemophilus 8 (1.6) 25 (4.9) 54 (2.1) 16 (2.7) 8 (1

influenzae
Haemophilus 0 10 (2.0) 0 0 0
parainfluenzae
Moraxella 0 6 (1.2) 4 (0.2) 0 1 (0

catarrhalis
Legionella 10 (1.9) Δ 87 (3.5) ◊ 21 (

pneumophila
Mycoplasma 27 (5.3) § 87 (17.2) § 32 (1.3) § ¥ 6 (1

pneumoniae
Chlamydia 10 (1.9) § 72 (14.2) § 32 (1.3) § ¥ 8 (1

pneumoniae
Coxiella 11 (2.1) § Δ 17 (0.7) § ¥ 2 (0

burnetii
Staphylococcus 1 (0.2) 6 (1.2) 18 (0.7) 25 (4.3) 6 (1

aureus
MSSA 1 (0.2) NR 9 (0.4) 18 (3.1) 4 (0
MRSA 0 NR 9 (0.4) 7 (1.2) 2 (0
Gram- 1 (0.2) 2 (0.4) 23 (0.9) 15 (2.6) 3 (0

negative
enteric bacilli
Pseudomonas 1 (0.2) 1 (0.2) 37 (1.5) 12 (2.1) 12 (

aeruginosa
Respiratory 15 (2.9) § † 123 (4.9) § † 10 (

viruses ‡
Other 6 (1.2) 14 (2.8) 33 (1.3) 8 (1.4) 15 (

pathogen
>1 pathogen 15 (2.9) ** 135 (5.4) 6 (1.0) 58 (
Diagnostic methods
Cultures (sputum, Cultures Cultures (sputum, Cultures Cult

blood, transthoracic (sputum, blood, transthoracic (blood, bloo
needle aspirate, blood), needle aspirate, endotracheal nee
transbronchial serologic transbronchial aspirates, tran
aspirates, BAL fluid, testing (for aspirates, BAL fluid, protected asp
protected specimen M. protected specimen specimen pro
brush respiratory pneumoniae, brush respiratory brush bru
samples, pleural C. samples, pleural respiratory sam
fluid), serologic pneumoniae) fluid), serologic samples, fluid
testing (for M. testing (for M. BAL fluid, test
pneumoniae, C. pneumoniae, C. pleural fluid), pne
pneumoniae, L. pneumoniae, L. urinary pne
pneumophila, C. pneumophila, C. antigen (for pne
burnetti, influenza A burnetti, influenza A L. burn
and B, parainfluenza and B, parainfluenza pneumophila) and
viruses 1 to 3, viruses 1 to 3, viru
respiratory syncytial respiratory syncytial resp
virus, adenovirus), virus, adenovirus), viru
urinary antigen urinary antigen urin
testing (for S. testing (for S. test
pneumoniae and L. pneumoniae and L. pne
pneumophila), pneumophila), pne
immunofluorescence immunofluorescence imm
assay plus virus assay plus virus assa
isolation or reverse isolation or reverse isol
transcriptase PCR for transcriptase PCR for tran
influenza A and B, influenza A and B, influ
parainfluenza parainfluenza par
viruses 1 to 3, viruses 1 to 3, viru
respiratory syncytial respiratory syncytial resp
virus, adenovirus virus, adenovirus viru
MSSA: methicillin-susceptible Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus;

NR: not reported; BAL: bronchoalveolar lavage; PCR: polymerase chain reaction.
* Results are reported as number of patients (percent). Different methods were used for diagnosis in
each study, as described in the row on diagnostic methods.
¶ Results are reported as the number of patients with a given pathogen, followed by the percentage
of patients in whom the pathogen was identified out of all of the patients in the study. For example, in
the first column, S. pneumoniae was detected in 30 of 507 patients in the study (5.9%). Among the 244
patients in whom a pathogen was identified, S. pneumoniae was detected in 12.3%.
Δ Testing for Legionella spp and C. burnetti was not performed.
◊ Legionella urinary antigen testing was performed in 35 ward patients and 26 intensive care unit
patients, but all results were negative. Legionella culture was not performed.
§ Pathogens detected by serologic methods may represent recent infection rather than active
infection.
¥ Testing for M. pneumoniae, C. pneumoniae, and C. burnetii was not performed.
‡ Influenza viruses A or B, parainfluenza viruses 1 to 3, respiratory syncytial virus, adenovirus.
† Testing for viruses was not performed.
** Some patients had >1 pathogen isolated, but the details were not reported.
References:
1. Cillóniz C, Ewig S, Polverino E, et al. Microbial aetiology of community-acquired pneumonia and its relation to severity.
Thorax 2011; 66:340.
2. Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Bnjidic Z. Etiology of community-acquired pneumonia treated in an
ambulatory setting. Resp Medicine 2005; 99:60.
3. Restrepo MI, Mortensen EM, Velez JA, et al. A comparative study of community-acquired pneumonia patients admitted
to the ward and the ICU. Chest 2008; 133:610.
Key differences from the 2019 American Thoracic Society and Infectious
Diseases Society of America (ATS/IDSA) guidelines for the treatment of adult
with community-acquired pneumonia (CAP)
ATS/IDSA outpatient CAP UpToDate CAP outpatient

Patient group empiric antibiotic empiric antibiotic
recommendations recommendations
Adult outpatients aged <65 The ATS/IDSA recommends UpToDate suggests amoxicillin
years, without comorbidities or amoxicillin monotherapy. For plus a macrolide or doxycycline
smoking, and who have not those who cannot use as preferred therapy because
used antibiotics within the prior penicillins, monotherapy with there is a potential morbidity
three months either a macrolide or benefit and the downside of a
doxycycline is recommended, short course of therapy for mos
provided local resistance rates patients is low.
among S. pneumoniae isolates
are <25%.*
Adult outpatients who meet any ATS/IDSA recommends either: UpToDate suggests combination
of the following criteria: Combination therapy with therapy with amoxicillin-
Age ≥65 years old a beta-lactam plus clavulanate plus a macrolide or
Active smoking macrolide or doxycycline doxycycline. Amoxicillin-
or clavulanate has reliable activity
Presence of comorbidities
against S. pneumoniae and an
(ie, chronic pulmonary, Monotherapy with a
overall favorable adverse effect
liver, heart, or kidney respiratory
profile.
disease; cancer, diabetes fluoroquinolone
mellitus, heart failure, or
There is no stated preference
alcohol use disorder)
between these regimens.
Antibiotic use within the
prior three months
Our approach is generally similar to the American Thoracic Society/Infectious Diseases Society of
America (ATS/IDSA) guidelines with few exceptions noted in this table. Refer to UpToDate text for
complete regimens, dosing, and rationale for antibiotic selection.
CAP: community-acquired pneumonia; ATS/IDSA: American Thoracic Society/Infectious Diseases

Society of America; S. pneumoniae: Streptococcus pneumoniae.
* For macrolides, resistance rates among S. pneumoniae are often >30% in the United States and
typically >25% for most parts of the world, apart from some regions in Northern Europe. For
doxycycline, resistance rates are less well established but are approximately 10 to 20% in the United
States and likely rising.
Reference:
1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An
Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J
Respir Crit Care Med 2019; 200:e45.
Community-acquired pneumonia: Empiric outpatient antibiotic selection in

adults
For all patients, our empiric regimens are designed to target: ◊

Streptococcus pneumoniae (most common bacterial CAP pathogen)
Atypical pathogens (eg, Legionella spp, Mycoplasma pneumoniae, Chlamydia pneumoniae)
Coverage is expanded in those with comorbidities, older age, or recent antibiotic use to include or
better treat:
Beta-lactamase-producing Haemophilus influenzae
Moraxella catarrhalis
Methicillin-susceptible Staphylococcus aureus
For patients with structural lung disease (eg, advanced COPD), coverage is further expanded to
include Enterobacteriaceae, such as Escherichia coli and Klebsiella spp.
ATS/IDSA: American Thoracic Society/Infectious Diseases Society of America; COPD: chronic

obstructive pulmonary disease; CAP: community-acquired pneumonia; IgE: immunoglobulin E.
* Major comorbidities include but are not limited to chronic heart, renal, or liver disease, diabetes
mellitus, asplenia, and immunosuppression.
¶ Patients with mild non-IgE-mediated reactions (eg, maculopapular rash) to penicillin or known
cephalosporin tolerance can generally use later-generation cephalosporins safely. Patients with IgE-
mediated reactions (hives, angioedema, anaphylaxis) or severe delayed reactions should generally
use other agents. Refer to the UpToDate text on penicillin hypersensitivity reactions for detail.
Δ Reasons to avoid macrolides include baseline prolonged QTc interval or risk for QTc prolongation
(eg, hypokalemia, hypomagnesemia, clinically significant bradycardia, or use of other QT-prolonging
agents).
◊ Our approach differs from the ATS/IDSA, which recommend monotherapy with amoxicillin,
doxycycline, or a macrolide (in areas where macrolide resistance is low) as options for patients
without comorbidities or risk factors for drug-resistant S. pneumoniae. By contrast, we prefer to treat
all patients with a regimen that treats most strains of drug-resistant S. pneumoniae and atypical
pathogens for all patients because the potential to reduce morbidity is high and the downside of a
short course of therapy for most patients is low. Refer to the UpToDate text for detail.
§ For macrolides, resistance rates among S. pneumoniae are often >30% in the United States and
typically >25% for most parts of the world, apart from some regions in Northern Europe. For
doxycycline, resistance rates are less well established but are approximately 10 to 20% in the United
States and likely rising.
¥ Lefamulin is a newer agent that is active against most CAP pathogens including S. pneumoniae, H.
influenzae, M. catarrhalis, S. aureus, and atypical pathogens. Although lefamulin lacks activity against
Enterobacteriaceae (eg, Klebsiella spp and E. coli) and thus is not appropriate for patients with
structural lung disease, its more targeted spectrum makes it less disruptive to the microbiome.
Clinical experience with lefamulin is limited, and it is not recommended in moderate to severe hepatic
dysfunction, pregnancy, breastfeeding, known long QT syndrome, or with concomitant QT-prolonging
agents. There are drug interactions with CYP3A4 and P-gp inducers and substrates; in addition,
lefamulin tablets are contraindicated with QT-prolonging CYP3A4 substrates. Refer to the Lexicomp
drug monograph and UpToDate text for detail.
‡ Omadacycline is another newer agent that is active against most CAP pathogens, including
Enterobacteriaceae. It is a potential alternative for patients who cannot tolerate beta-lactams (or
other agents) and want to avoid fluoroquinolones.
Recommended antimicrobial therapy for specific pathogens causing

community-acquired pneumonia in adults
Alternative
Organism Preferred antimicrobial(s)
antimicrobial(s)
Streptococcus pneumoniae
Penicillin nonresistant; Penicillin G, amoxicillin Macrolide, cephalosporins (oral

MIC <2 mcg/mL* [cefpodoxime, cefprozil,
cefuroxime, cefdinir] or
parenteral [cefuroxime,
ceftriaxone, cefotaxime]),
clindamycin, doxycycline,
respiratory fluoroquinolone ¶
Penicillin resistant; MIC Agents chosen on the basis of Vancomycin, linezolid, high-dose
≥2 mcg/mL* susceptibility, including amoxicillin (3 g/day with
cefotaxime, ceftriaxone, penicillin MIC ≤4 mcg/mL)
fluoroquinolone
Haemophilus influenzae
Non-beta-lactamase Amoxicillin Fluoroquinolone, doxycycline,

producing azithromycin, clarithromycin Δ
Beta-lactamase producing Second- or third-generation Fluoroquinolone, doxycycline,

cephalosporin, amoxicillin- azithromycin, clarithromycin Δ
clavulanate
Mycoplasma Macrolide, a tetracycline Fluoroquinolone

pneumoniae/Chlamydophila
pneumoniae
Legionella species Fluoroquinolone, azithromycin Doxycycline
Chlamydophila psittaci A tetracycline Macrolide
Coxiella burnetii A tetracycline Macrolide
Francisella tularensis Doxycycline Gentamicin, streptomycin
Yersinia pestis Streptomycin, gentamicin Doxycycline, fluoroquinolone
Bacillus anthracis (inhalation) Ciprofloxacin, levofloxacin, Other fluoroquinolones; beta-

doxycycline (usually with second lactam, if susceptible; rifampin;
agent) clindamycin; chloramphenicol
Enterobacteriaceae Third-generation cephalosporin, Beta-lactam-beta-lactamase

carbapenem ◊ (drug of choice if inhibitor § , fluoroquinolone
extended-spectrum beta-
lactamase producer)
Pseudomonas aeruginosa Antipseudomonal beta-lactam ¥ Aminoglycoside plus

plus (ciprofloxacin or (ciprofloxacin or levofloxacin ‡ )
levofloxacin ‡ or aminoglycoside)
Burkholderia pseudomallei Carbapenem, ceftazidime Fluoroquinolone, TMP-SMX
Acinetobacter species Carbapenem Cephalosporin-aminoglycoside,

ampicillin-sulbactam, colistin
Staphylococcus aureus
Methicillin susceptible Antistaphylococcal penicillin † Cefazolin, clindamycin
Methicillin resistant Vancomycin or linezolid TMP-SMX
Bordetella pertussis Macrolide TMP-SMX
Anaerobe (aspiration) Beta-lactam-beta-lactamase Carbapenem

inhibitor § , clindamycin
Influenza virus Refer to associated topic

reviews**
Mycobacterium tuberculosis Isoniazid plus rifampin plus Depends on susceptibility

ethambutol plus pyrazinamide pattern; refer to associated topi
reviews
Coccidioides species For uncomplicated infection in a Amphotericin B

normal host, no therapy
generally recommended; for
therapy, itraconazole,
fluconazole
Histoplasmosis Itraconazole ¶¶ Amphotericin B ¶¶
Blastomycosis Itraconazole ¶¶ Amphotericin B ¶¶
Choices should be modified on the basis of susceptibility test results and advice from local specialists.
Refer to local references for appropriate doses.
Preferred agent may change over time due to changing resistance patterns and depends on many
factors, including severity of illness. Refer to associated UpToDate topic reviews for updated and
detailed treatment recommendations for each pathogen.
MIC: minimum inhibitory concentration; ATS: American Thoracic Society; CDC: United States Centers
for Disease Control and Prevention; IDSA: Infectious Diseases Society of America; TMP-SMX:
trimethoprim-sulfamethoxazole.
* The 2 mcg/mL threshold is for nonmeningitis dosing. The threshold is lower for meningitis dosing.
¶ Levofloxacin, moxifloxacin, gemifloxacin (not a first-line choice for penicillin-susceptible strains);

ciprofloxacin is appropriate for Legionella and most gram-negative bacilli (including H. influenzae).
Δ Azithromycin is more active in vitro than clarithromycin for H. influenzae.
◊ Imipenem-cilastatin, meropenem, ertapenem.
§ Piperacillin-tazobactam, ampicillin-sulbactam, ticarcillin-clavulanate (not available in the United

States), or amoxicillin-clavulanate.
¥ Ceftazidime, cefepime, aztreonam, imipenem, meropenem, or piperacillin (not available in the

United States).
‡ 750 mg daily.
† Nafcillin, oxacillin, flucloxacillin.
** Choice of antiviral regimen depends on type of influenza virus and expected resistance pattern.
(Refer to the UpToDate topic on antiviral drugs for the treatment of influenza in adults.)
¶¶ Preferred agent depends on severity of illness. Refer to associated UpToDate topic reviews for full
discussions.
Adapted with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American
Thorac Society Consensus Guidelines on the Management of Community-acquired Pneumonia in Adults. Clin Infect Dis 2007;
44:S27. Copyright © 2007 University of Chicago Press.
Usual duration of findings in treated community-acquired pneumonia
Abnormality Duration (days)
Tachycardia and hypotension 2
Fever, tachypnea, and hypoxia 3
Cough 14
Fatigue 14
Infiltrates on chest radiograph 30
References:
1. Marrie TJ, Beecroft MD, Herman-Gnjidic Z. Resolution of symptoms in patients with community-acquired pneumonia
treated on an ambulatory basis. J Infect 2004; 49:302.
2. Metlay JP, Atlas SJ, Borowsky LH, Singer DE. Time course of symptom resolution in patients with community-acquired
pneumonia. Respir Med 1998; 92:1137.
3. Fine MJ, Stone RA, Singer DE, et al. Processes and outcomes of care for patients with community-acquired pneumonia:
results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study. Arch Intern Med 1999; 159:970.
Type of drug reactions
Type of reaction Common features
Non-allergic reaction Adverse effects (eg, diarrhea, vomiting, yeast vaginitis)

Family history of penicillin allergy but no personal history
Mild non-IgE-mediated Maculopapular rash (with or without itching)

reaction Medical record lists penicillin allergy but patient unaware of reaction
IgE-mediated reaction Anaphylaxis

Angioedema
Wheezing
Laryngeal edema
Hypotension
Hives/urticaria
Serious delayed reactions Toxic epidermal necrolysis (TEN)

Stevens-Johnson syndrome (SJS)
Drug reaction with eosinophilia and systemic symptoms/drug-
induced hypersensitivity syndrome (DRESS/DiHS)
Other exfoliating dermatoses/erythroderma
Serum sickness-like reactions
Drug-induced cytopenias
Drug-induced renal, hepatic, or other specific organ damage
IgE: immunoglobulin E.

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21/2/24, 20:12 Treatment of community-acquired pneumonia in adults in the outpatient setting - UpToDate

Official reprint from UpToDate®

Treatment of community-acquired pneumonia in adults

Literature review current through: Jan 2024.

Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary

● (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in

● (See "Community-acquired pneumonia in adults: Assessing severity and determining

● (See "Treatment of community-acquired pneumonia in adults who require

● (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)

● (See "Epidemiology, pathogenesis, and microbiology of community-acquired

● (See "Aspiration pneumonia in adults" and "Epidemiology of pulmonary infections in

Health care-associated pneumonia (HCAP; no longer used) referred to pneumonia acquired

● Establishing the diagnosis – The diagnosis of CAP generally requires the

evaluation and diagnostic testing for community-acquired pneumonia in adults",

While the combination of a compatible clinical syndrome and imaging findings

EMPIRIC ANTIBIOTIC TREATMENT

● Coverage is expanded to include or better treat certain gram-negative pathogens (eg,

Generally, we add either a macrolide or doxycycline to the beta-lactam to target atypical

antiviral treatment is typically warranted. (See "Seasonal influenza in nonpregnant adults:

● For patients with mild non-immunoglobulin (Ig)E-mediated reactions to penicillin (eg

● When amoxicillin-clavulanate cannot be used (eg, due to allergy or other intolerance), a

● Despite its greater convenience, we reserve monotherapy with respiratory

Caveats for fluoroquinolones and macrolides — Although fluoroquinolones are frequently

Pathogen-directed therapy is less common in the outpatients setting because microbiologic

adults" and "Treatment and prevention of Legionella infection" and "Pseudomonas

● COVID-19 – Patients with COVID-19 and pneumonia should generally be hospitalized

LIMITED ROLE FOR GLUCOCORTICOIDS

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) commonly co-occur

exacerbations: Management", section on 'Home or office management of COPD

Chest radiograph — We do not routinely obtain a follow-up chest radiograph in patients

● Loculated infection – Patients with complications such as lung abscess, empyema, or

● Bronchial obstruction – Bronchial obstruction (eg, by a tumor) can cause a

● Pathogens that cause subacute/chronic CAP – M. tuberculosis, nontuberculous

● Incorrect initial diagnosis – Failure to improve also raises the possibility of an

Once a patient is characterized as having nonresolving CAP, a complete, new physical

Pneumococcal and influenza vaccination — Vaccination is an effective and important

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: Pneumonia in adults (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Epidemiology – Community-acquired pneumonia (CAP) is one of the most common

● The importance of S. pneumoniae – The backbone of therapy is the beta-lactam, which

● Our approach to empiric antibiotic selection – Selection of a specific regimen

Our approach is generally similar to the American Thoracic Society/Infectious Diseases

● Fluoroquinolones and other alternative agents – Fluoroquinolone monotherapy is

● Duration of therapy – A five-day course of antibiotic therapy is sufficient for most

UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed on

Use of UpToDate is subject to the Terms of Use.

1. File TM. Community-acquired pneumonia. Lancet 2003; 362:1991.

2. Wunderink RG, Waterer GW. Clinical practice. Community-acquired pneumonia. N Engl J

7. Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not

Database Syst Rev 2012; :CD004418.

28. Raz-Pasteur A, Shasha D, Paul M. Fluoroquinolones or macrolides alone versus

34. López-Alcalde J, Rodriguez-Barrientos R, Redondo-Sánchez J, et al. Short-course versus

Classification by site of acquisition

Community-acquired An acute infection of the pulmonary parenchyma acquired outside of

Nosocomial pneumonia An acute infection of the pulmonary parenchyma acquired in hospital