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Treatment of community-acquired pneumonia in adults in the outpatient setting

Author: Thomas M File, Jr, MD

Section Editors: John G Bartlett, MD, Julio A Ramirez, MD, FACP
Deputy Editor: Sheila Bond, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Feb 2018. | This topic last updated: Jun 19, 2017.

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 [1-4]. It is associated with considerable morbidity and mortality, particularly in older adult patients and those with
major comorbidities. (See "Prognosis of community-acquired pneumonia in adults".)

The treatment of CAP in adults in the outpatient setting will be reviewed here. A variety of other important issues related to CAP are discussed separately. These
include:

● The diagnostic approach to patients with CAP. (See "Diagnostic approach to community-acquired pneumonia in adults".)

● How one makes the decision to admit patients with CAP to the hospital. (See "Community-acquired pneumonia in adults: Assessing severity and determining
the appropriate site of care".)

● Treatment recommendations for CAP in patients requiring hospitalization. (See "Treatment of community-acquired pneumonia in adults who require
hospitalization".)

● Treatment recommendations for patients with healthcare-associated pneumonia. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in
adults".)

● The evidence for efficacy of different antibiotic medications in the empiric treatment of CAP and issues related to drug resistance. (See "Antibiotic studies for
the treatment of community-acquired pneumonia in adults".)

● The epidemiology and microbiology of CAP. (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults".)

● Pneumonia in special populations, such as aspiration pneumonia and immunocompromised patients. (See "Aspiration pneumonia in adults" and "Pulmonary
infections in immunocompromised patients".)

MANAGEMENT OF HEALTHCARE-ASSOCIATED PNEUMONIA — As noted above, 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).

A third category of pneumonia, designated healthcare-associated pneumonia (HCAP), was included in prior HAP guidelines [5] (but not current HAP guidelines [6]) to
identify patients thought to be at increased risk for multidrug-resistant (MDR) pathogens coming from community settings. HCAP referred to pneumonia acquired in
healthcare facilities such as nursing homes, hemodialysis centers, and outpatient clinics. The rationale for the separate designation of HCAP (and its association
with HAP) was that patients with HCAP were thought to be at higher risk for MDR organisms. However, several studies have shown that many patients defined as
having HCAP are not at high risk for MDR pathogens [7-9]. Furthermore, although interaction with the healthcare system is potentially a risk for MDR pathogens,
underlying patient characteristics are also important independent determinants of risk for MDR pathogens. It is anticipated that patients previously designated as
HCAP will be included in the next update of the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) CAP guidelines because patients
with HCAP frequently present from the community and are initially cared for in emergency departments.

For these reasons, we feel that patients previously classified as having HCAP should be managed in a similar way to those with CAP, with the need for therapy
targeting MDR 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 [10,11].

DETERMINING THE APPROPRIATE SITE OF CARE — Determining whether a patient with community-acquired pneumonia (CAP) can be safely treated as an
outpatient or requires admission to an observation unit, general medical ward, or higher acuity level of inpatient care, such as an intensive care unit (ICU), is an
essential first step of medical management that will help inform downstream diagnostic and therapeutic decisions (algorithm 1). Severity of illness is the most
critical factor in making this determination, but 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 healthcare facility that precludes timely return to care in the event of clinical worsening).

Prediction rules have been developed to assist in the decision of site of care for CAP. Of the available rules, we strongly prefer the Pneumonia Severity Index (PSI)
(calculator 1) because it is the most accurate and its safety and effectiveness in guiding clinical decisionmaking have been empirically confirmed. The CURB-65
score (calculator 2) is an alternative that can be used when a less complex scoring system for prognosis is desired, but its safety and effectiveness in guiding the
initial site of treatment have not been empirically assessed. Clinical judgment should be used for all patients, incorporating the prediction rule scores as a
component of the decision for hospitalization or ICU admission but not as an absolute determinant [12].

The approach to site of care is discussed in greater detail elsewhere. (See "Community-acquired pneumonia in adults: Assessing severity and determining the
appropriate site of care", section on 'Approach to site of care'.)

In a retrospective cohort study of over one million Medicare beneficiaries (aged >64 years) admitted to hospitals in the United States with pneumonia, ICU admission
for patients with disease of marginal severity was associated with improved survival and no difference in costs compared with general ward admission, suggesting
that ICU admission may benefit such patients [13]. Patients living closer than the median differential distance (<3.3 miles) to a hospital with high ICU admission rates
were significantly more likely to be admitted to the ICU than patients living farther away (36 versus 23 percent). Because most ill patients with pneumonia will seek
care at the nearest hospital, patients who live close to a hospital with high ICU admission rates are more likely to be admitted to the ICU on a discretionary basis. In
adjusted analyses, for the 13 percent of patients whose admission appeared to be discretionary (dependent only on distance), ICU admission was associated with a
significantly lower adjusted 30-day mortality than patients admitted to a general ward (14.8 versus 20.5 percent). There were no differences in Medicare spending or
hospitalization costs between the two groups. These results suggest a potential benefit of using broader ICU admission criteria but should be confirmed in a
randomized trial.

PRINCIPLES OF ANTIMICROBIAL THERAPY — Community-acquired pneumonia (CAP) can be caused by a variety of pathogens. The most common bacterial cause
is Streptococcus pneumoniae, for which the choice of initial antimicrobial therapy is complicated by the emergence of antibiotic resistance. The increasing availability
of molecular tests has increased identification of respiratory viruses in CAP in adults. A study in the United States indicates that viruses are a common cause of
pneumonia in adults admitted to the hospital [14]. Empiric antimicrobial therapy is directed against the most common bacterial etiologies (table 1) [2,15,16]. (See
"Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology' and "Antibiotic studies for the treatment of
community-acquired pneumonia in adults", section on 'Drug resistance and choice of therapy'.)

Establishing the diagnosis — The diagnosis of CAP should be established before empiric therapy is started. The presence of an infiltrate on plain chest radiograph is
considered the gold standard for diagnosing pneumonia when clinical (and, in some cases, microbiologic) features are supportive. A chest radiograph should be
obtained in patients with suspected pneumonia when possible; a demonstrable infiltrate by chest radiograph or other imaging technique is required for the diagnosis
of pneumonia, according to the 2007 consensus guidelines from the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) [2].
(See "Diagnostic approach to community-acquired pneumonia in adults", section on 'Radiologic evaluation'.)

The sputum Gram stain can be useful for directing the choice of initial therapy if performed on a good quality sample and interpreted by skilled examiners using
appropriate criteria [2]. Other diagnostic tests are discussed in detail separately. (See "Diagnostic approach to community-acquired pneumonia in adults", section on
'Diagnostic testing for microbial etiology'.)

The 2007 IDSA/ATS guidelines on the management of CAP suggest that routine tests to identify an etiology for CAP are optional for patients who do not require
hospitalization [2]. This recommendation is based in part upon the low rate of failure of empiric therapy in patients with CAP treated in the outpatient setting. The
efficacy of empiric therapy was illustrated in a study of over 700 ambulatory patients treated for CAP in one of six emergency departments seen from November
2000 through April 2001, in which empiric antibiotics (a macrolide or fluoroquinolone in >88 percent) were almost universally effective, with only 2.2 percent requiring
hospitalization within three weeks of initial emergency department visit [17].

In contrast, testing for a microbial diagnosis is important in clinical or epidemiologic settings, suggesting possible infection with an organism that requires treatment
different from standard empiric regimens. These 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 [2]. Advances in molecular testing for
etiology may allow for earlier pathogen-directed therapy than was previously possible. (See "Diagnostic approach to community-acquired pneumonia in adults" and
"Sputum cultures for the evaluation of bacterial pneumonia", section on 'Community-acquired pneumonia'.)

Empiric therapy — Antibiotic therapy is typically begun on an empiric basis, since the causative organism is not identified in an appreciable proportion of cases of
CAP treated in the outpatient setting (table 1) [2,18]. The clinical features and chest radiographic findings are not sufficiently specific to determine etiology and
influence treatment decisions. Antibiotics should be started as soon as possible once the diagnosis of CAP is established. 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. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Timing of antimicrobial initiation'.)

The selection of antimicrobial regimens for empiric therapy is based upon a number of factors, including:

● The most likely pathogen(s), taking into account local epidemiology, travel history, and other epidemiologic and clinical clues. (See 'Common pathogens' below.)

● Clinical trials proving efficacy. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults".)

● Risk factors for antimicrobial resistance. The choice of empiric therapy must take into account the emergence of antibiotic resistance among S. pneumoniae,
one of the most common bacteria responsible for CAP. (See 'Risk factors for drug resistance' below.)

● Medical comorbidities that may influence the likelihood of a specific pathogen and that may be a risk factor for treatment failure.

Additional factors that may affect the choice of antimicrobial regimen include the potential for inducing antimicrobial resistance, pharmacokinetic and
pharmacodynamic properties, safety profile, and cost [19].

Specific regimens are provided below. (See 'Treatment regimens' below.)

Common pathogens — Although a variety of bacterial pathogens can cause CAP, a limited number are responsible for the majority of cases. Using the usual
diagnostic testing methods, the etiology is not determined in most cases. Advances in molecular testing for etiology may allow for earlier pathogen-directed therapy.
(See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Microbiology'.)

With respect to patients treated in the outpatient setting, the most frequently detected pathogens are S. pneumoniae, Mycoplasma pneumoniae, and respiratory
viruses (eg, influenza, parainfluenza, respiratory syncytial virus) (table 1). Legionella pneumophila and Haemophilus influenzae are less common. The "atypical"
pathogens are not often identified in clinical practice because there are not specific, rapid, or standardized tests for their detection, with the exception of L.
pneumophila. (See "Clinical manifestations and diagnosis of Legionella infection".)

Patients with CAP due to S. aureus, Enterobacteriaceae, and Pseudomonas aeruginosa are typically sicker and require admission to the hospital. (See "Treatment of
community-acquired pneumonia in adults who require hospitalization", section on 'Likely pathogens'.)

Local epidemiology, travel history, and other epidemiologic and clinical clues should also be considered when selecting an empiric regimen. Specifically, patients
should be queried about risk for drug-resistant S. pneumoniae and travel to areas associated with specific pathogens (eg, Arabian peninsula for Middle East
respiratory syndrome). (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Epidemiologic clues'.)

Risk factors for drug resistance — Risk factors for and other issues related to drug resistance in patients with CAP are discussed in detail elsewhere. (See "Antibiotic
studies for the treatment of community-acquired pneumonia in adults", section on 'Drug resistance and choice of therapy'.)

Summarized briefly, risk factors for drug-resistant S. pneumoniae in adults include:

 ● Age >65 years

● Beta-lactam, macrolide, or fluoroquinolone therapy within the past three to six months

● Alcoholism

● Medical comorbidities

● Immunosuppressive illness or therapy

● Exposure to a child in a daycare center

Recent therapy or a repeated course of therapy with beta-lactams, macrolides, or fluoroquinolones is a risk factor for pneumococcal resistance to the same class of
antibiotic [20].

The impact of discordant drug therapy, which refers to treatment of an infection with an antimicrobial agent to which the causative organism has demonstrated in
vitro resistance, appears to vary with antibiotic class and possibly with specific agents within a class. Most studies have been performed in patients with S.
pneumoniae infection and suggest that current levels of beta-lactam resistance generally do not cause treatment failure when appropriate agents (eg, amoxicillin,
ceftriaxone, cefotaxime) and doses are used. Of the beta-lactams, cefuroxime is a possible exception. In addition, there appears to be an increased risk of macrolide
failure in patients with macrolide-resistant S. pneumoniae. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on
'Outcomes with discordant drug therapy' and "Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamides, and ketolides", section on
'Macrolides and azalides'.)

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 it is known that there is a high local prevalence of both macrolide-resistant and
doxycycline-resistant S. pneumoniae and that an alternative regimen 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 Clostridium difficile colitis [21]. 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 [17]. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on
'Fluoroquinolone resistance' and "Clostridium difficile infection in adults: Epidemiology, microbiology, and pathophysiology", section on 'Antibiotic use'.)

A major limitation of macrolides is that in some regions of the world, including the United States, the overall prevalence of macrolide-resistant S. pneumoniae (high
level and low level) is now >25 percent; in the United States, it is >40 percent. (See "Resistance of Streptococcus pneumoniae to the macrolides, azalides,
lincosamides, and ketolides", section on 'Macrolides and azalides'.)

Both the macrolides and the 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, clarithromycin, and telithromycin", 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 "Fluoroquinolones", section on 'QT interval
prolongation and arrhythmia' and "Azithromycin, clarithromycin, and telithromycin", section on 'QT interval prolongation and cardiovascular events' and "Acquired long
QT syndrome: Definitions, causes, and pathophysiology" and "Pharmacology of azoles", section on 'Selected clinical effects'.)

GUIDELINES — A number of medical societies have issued guidelines for the treatment of community-acquired pneumonia (CAP) [2,22-24]. The antibiotic regimens
advocated by a collaboration between the Infectious Disease Society of America (IDSA) and the American Thoracic Society (ATS) in 2007 [2] and guidelines from the
British Thoracic Society (BTS) in 2009 [22] are summarized in the tables (table 2 and table 3). Both guidelines note problems with the emergence of drug-resistant S.
pneumoniae. Links to guidelines are provided separately. (See 'Society guideline links' below.)

The following discussion will review empiric antibiotic therapy in ambulatory patients with CAP. Guideline recommendations for therapy of patients with CAP treated
in the inpatient setting are presented separately. (See "Treatment of community-acquired pneumonia in adults who require hospitalization".)

● The regimens chosen by the IDSA/ATS guidelines mainly rely on macrolides (with or without a beta-lactam) or newer fluoroquinolones for outpatient therapy
(table 2) [2]. The guidelines promote the use of macrolides to provide coverage for both S. pneumoniae and atypical pathogens (particularly, M. pneumoniae and
C. pneumoniae), which account for the majority of cases of CAP in ambulatory patients (table 1). In studies from different regions of the world, atypical
pathogens account for 20 to 30 percent of cases of CAP [25].

The IDSA/ATS guidelines recommend not using macrolide monotherapy in settings in which the prevalence of high-level macrolide resistance among S.
pneumoniae is ≥25 percent [2]. However, some studies have suggested that even with low-level resistance, treatment failure with macrolide monotherapy is more
likely [26,27]. We therefore avoid macrolide monotherapy for empiric therapy when the overall prevalence of macrolide resistance (high level and low level)
among S. pneumoniae is ≥25 percent. It is also important to note that in some regions of the world, including the United States, the prevalence of high-level
macrolide-resistant S. pneumoniae is now approximately 20 percent and the overall prevalence of macrolide-resistant S. pneumoniae (high level and low level) is
>40 percent. When such resistance is present, a macrolide should not be used as monotherapy for empiric therapy. (See "Antibiotic studies for the treatment of
community-acquired pneumonia in adults", section on 'Macrolide resistance' and "Resistance of Streptococcus pneumoniae to the macrolides, azalides,
lincosamides, and ketolides", section on 'Macrolides and azalides'.)

Appropriate regimens are discussed below. (See 'Comorbidities or recent antibiotic use' below.)

● The BTS and the United Kingdom's National Institute for Health and Care Excellence (NICE) guidelines tend to select older antibiotics than those recommended
in North America (table 3) [22,24].

North America — In the 2007 IDSA/ATS guidelines, the macrolides, which are effective against the atypical pathogens, were recommended in those without
significant risk factors for macrolide-resistant S. pneumoniae. Experience in North America suggests that macrolide-resistant S. pneumoniae is less common in
patients without comorbidities or risk factors compared with patients with risk factors [19,26,28]. Recent use of antibiotics is considered a risk factor for resistant S.
pneumoniae; thus, monotherapy with a macrolide is not recommended for persons who received an antibiotic in the preceding three months.

As noted above, since the overall rate of macrolide resistance (high level and low level) among S. pneumoniae is >25 percent in virtually all areas of the United States
and in certain other regions worldwide, we recommend not using monotherapy with a macrolide for empiric therapy in such regions if the diagnosis of CAP has been
established. (See 'Guidelines' above and "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Macrolide resistance' and
"Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamides, and ketolides", section on 'Macrolides and azalides'.)

United Kingdom — In the 2009 British Thoracic Society guidelines, the preferred drug for outpatient management is amoxicillin (500 mg orally three times daily), with
doxycycline or clarithromycin as alternatives (eg, for those with penicillin allergy) (table 3) [22].The 2014 NICE guidelines make similar recommendations [24].

The rationale is that amoxicillin at these doses is effective against most strains of S. pneumoniae with decreased susceptibility to penicillin. Most of the macrolide-
resistant S. pneumoniae in Europe is erm-mediated high-level resistance. As a result, the macrolides are not optimal first-line empiric agents. (See "Antibiotic studies
for the treatment of community-acquired pneumonia in adults", section on 'Macrolide resistance' and "Resistance of Streptococcus pneumoniae to the macrolides,
azalides, lincosamides, and ketolides".)

Coverage of atypical pathogens — The United Kingdom approach places less significance than the North American approach on the need to treat the atypical
pathogens empirically in ambulatory patients [2,22,24]. Initial empiric therapy that covers M. pneumoniae is considered unnecessary, since the pathogen exhibits
epidemic periodicity every four to five years and largely affects younger persons.

Although the clinical course of M. pneumoniae or C. pneumoniae infection is often self-limited, these pathogens can cause severe CAP. As a result, it has been argued
that appropriate treatment for even mild CAP due to Mycoplasma reduces both morbidity and the duration of symptoms [29]. (See "Mycoplasma pneumoniae
infection in adults".)

The efficacy of empiric coverage of atypical pathogens was evaluated in a 2005 meta-analysis that evaluated 18 randomized trials of over 6700 patients with mild to
moderate CAP who were assigned to treatment with either a beta-lactam or an antibiotic active against atypical pathogens [30]. There was no overall advantage to
covering atypical pathogens in terms of the rate of failure to achieve clinical cure or improvement (relative risk [RR] 0.97, 95% CI 0.87-1.07) but, in a subgroup
analysis, there was a significantly lower failure rate for Legionella infection with such a regimen (RR 0.40, 95% CI 0.19-0.85). These trials were not designed to
compare the time to response with the different regimens.

TREATMENT REGIMENS — Empiric treatment regimens for outpatients with community-acquired pneumonia (CAP) are based upon studies of the effectiveness of
antibiotics, the severity of illness, the presence of comorbid conditions, and the prevalence of risk factors for drug-resistant S. pneumoniae (algorithm 2) [2].

It is important to note that treatment for CAP should only be given to patients in whom the diagnosis of CAP has been established; a demonstrable infiltrate by chest
radiograph or other imaging technique is required for the diagnosis of pneumonia [2]. (See 'Establishing the diagnosis' above and "Diagnostic approach to
community-acquired pneumonia in adults".)

There are several important caveats regarding fluoroquinolones and macrolides, which are discussed above. (See 'Caveats for fluoroquinolones and macrolides'
above.)

The doses given below are intended for patients with normal renal function; the doses of certain agents should be reduced in patients with renal dysfunction.

No comorbidities, no recent antibiotic use — For patients without major comorbidities or recent antibiotic use, antibiotic selection for outpatient treatment of CAP
depends on the local prevalence of macrolide resistance among S. pneumoniae isolates (algorithm 2), as outlined in the following sections. (See 'Low rate (<25
percent) of macrolide resistance' below and 'High rate (≥25 percent) of macrolide resistance (includes United States)' below.)

In general, patients without major comorbidities or recent antibiotic use do not have host risk factors for macrolide-resistant infection. However, in some regions of
the world, the overall prevalence of macrolide-resistant S. pneumoniae (high level and low level) is now >25 percent; in the United States, it exceeds 40 percent. In
such cases, the risk of a macrolide-resistant S. pneumoniae infection, even in otherwise healthy individuals without antibiotic use, is high enough that we recommend
that a macrolide not be used as empiric monotherapy. (See "Resistance of Streptococcus pneumoniae to the macrolides, azalides, lincosamides, and ketolides",
section on 'Macrolides and azalides'.)

Low rate (<25 percent) of macrolide resistance — For CAP in patients who do not require hospitalization, have no major comorbidities, have not used antibiotics
within the last three months, and reside in a region in which there is not a high prevalence of macrolide-resistant S. pneumoniae (<25 percent; which does not include
the United States), we recommend one of the following oral macrolides:

● Azithromycin – 500 mg on day 1 followed by four days of 250 mg a day or 500 mg daily for three days

● Clarithromycin – 500 mg twice daily for five days

● Clarithromycin XL – Two 500 mg tablets (1000 mg per dose) once daily for five days

Doxycycline is another option, but we prefer a macrolide over doxycycline because there are more data demonstrating the efficacy of macrolides for uncomplicated
CAP. However, for nonpregnant patients who cannot take azithromycin due to a contraindication (eg, increased risk of QT interval prolongation, allergy), doxycycline
(100 mg orally twice daily) is an appropriate alternative. If the local rate of doxycycline resistance among S. pneumoniae is known to be ≥25 percent, options include
the regimens listed below for patients with major comorbidities or recent antibiotic use. (See 'Comorbidities or recent antibiotic use' below.)

Appropriate regimens are also summarized in the following algorithm (algorithm 2).

High rate (≥25 percent) of macrolide resistance (includes United States) — For patients with CAP who do not require hospitalization, have no major
comorbidities, and have not used antibiotics within the last three months but for whom a macrolide is not recommended due to a high local rate (≥25 percent) of
macrolide-resistant S. pneumoniae, we generally suggest doxycycline (100 mg orally twice daily) (algorithm 2). However, if the patient lives in a region where the local
rate of doxycycline resistance among S. pneumoniae is ≥25 percent or cannot take doxycycline for another reason (eg, pregnancy), options include the regimens
recommended for patients with major comorbidities or recent antibiotic use (ie, a combination beta-lactam regimen or a fluoroquinolone). (See 'Comorbidities or
recent antibiotic use' below.)
Local rates of doxycycline-resistant S. pneumoniae are not readily available to most clinicians, but clinicians may be able to determine the local rates of resistance
among S. pneumoniae by consulting with their local hospital's microbiology laboratory. Available data suggest the rate of doxycycline-resistant S. pneumoniae is
lower than the rate of macrolide-resistant S. pneumoniae. (See "Resistance of Streptococcus pneumoniae to the fluoroquinolones, doxycycline, and trimethoprim-
sulfamethoxazole", section on 'Prevalence of resistance'.)

There are in vitro data to support the use of doxycycline for CAP in settings with low rates of resistance, but there are few clinical data. If doxycycline is used,
patients should be followed closely for lack of clinical response. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on
'Doxycycline'.)

Comorbidities or recent antibiotic use — The risk of infection with resistant pathogens is higher in patients who have a major comorbidity (ie, chronic obstructive
pulmonary disease [COPD], liver or renal disease, cancer, diabetes, congestive heart failure, alcoholism, or immunosuppression), have used antibiotics within the
prior three months, or live in a region with a substantial incidence of macrolide-resistant and doxycycline-resistant S. pneumoniae (≥25 percent).

For such patients, we recommend one of the following regimens:

● Combination therapy with a beta-lactam effective against S. pneumoniae (preferred agents: high-dose amoxicillin 1 g three times daily or amoxicillin-clavulanate
XR 2 g twice daily; alternative agents: cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily, but in vitro data suggest that they are less active
against S. pneumoniae than amoxicillin) PLUS either a macrolide (azithromycin 500 mg on day 1 followed by four days of 250 mg a day or clarithromycin 500 mg
twice daily or clarithromycin XL 1000 mg once daily) or doxycycline (100 mg twice daily). Treatment should generally be continued for five days. (See 'Treatment
duration and response' below.)

● A respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily or gemifloxacin 320 mg daily) for five days. (See 'Treatment duration and
response' below.)

Appropriate regimens are also summarized in the following algorithm (algorithm 2).

The greater convenience of fluoroquinolone monotherapy must be balanced against the severity of adverse effects (including the risk for C. difficile infection) and the
risk of selection for resistance in colonizing organisms, which are generally thought to be greater with fluoroquinolones. These issues are discussed in greater detail
above. (See 'Caveats for fluoroquinolones and macrolides' above.)

As noted above, for nonpregnant patients with known QT interval prolongation or risk factors for QT interval prolongation, we favor combination therapy with a beta-
lactam plus doxycycline in order to avoid the QT interval-prolonging effects of fluoroquinolones and macrolides. (See 'No comorbidities, no recent antibiotic use'
above.)

Because azithromycin is more effective in vitro against most strains of H. influenzae than clarithromycin, azithromycin is preferred over clarithromycin for outpatients
with comorbidities such as chronic obstructive pulmonary disease [2].

Pathogen-directed therapy — If the etiology of CAP has been identified using reliable microbiologic methods, antimicrobial therapy should be directed at that
pathogen (table 4) [2].

Pathogen-specific therapy for selected pathogens is discussed separately. (See "Pneumococcal pneumonia in adults" 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".)

Treatment duration and response — With respect to treatment duration, we generally agree with the 2007 Infectious Diseases Society of America/American Thoracic
Society guidelines [2]. Most ambulatory patients with CAP should be treated for five days, including those receiving azithromycin 500 mg on the first day followed by
250 mg daily on subsequent days and those receiving any other antibiotic. Because of its long half-life, patients 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.

Two meta-analyses of randomized trials of patients with mild to moderate CAP found comparable clinical outcomes with less than seven days compared with more
than seven days of antimicrobial therapy [31,32]. One of the meta-analyses included trials in which short courses of azithromycin were compared with longer courses
of therapy of other agents [31]; this is important to note since azithromycin has a long half-life, and therefore a short duration of therapy does not necessarily
translate into a short period of antimicrobial activity. However, the second meta-analysis did not include trials in which azithromycin was used and compared
treatment with the same agents but for different durations of therapy and suggested that a short course of these other antimicrobial agents is sufficient for mild to
moderate CAP [32]. (See "Antibiotic studies for the treatment of community-acquired pneumonia in adults", section on 'Duration of therapy'.)

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 often persist as the patient convalesces (table 5) [33-35]. This was illustrated in a study of sequential
interviews in 134 ambulatory patients with CAP [33]. 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 [35].

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 [34]. (See "Prognosis of community-acquired pneumonia in adults", section
on 'Mortality and symptom resolution'.)

Persistence of such symptoms is not an indication to extend the course of antibiotic therapy as long as the patient has demonstrated some clinical response to
treatment [2]. Patients who have not responded to therapy after 48 to 72 hours should be reevaluated. (See "Nonresolving pneumonia".)

Clinical follow-up — All patients who are treated for CAP at home should have a follow-up visit or communication with a healthcare provider within 24 to 48 hours
after being diagnosed to determine whether they are feeling better and assess whether any complications of pneumonia have developed. In addition, a later visit is
often indicated to assess for resolution of pneumonia.

Follow-up chest radiograph — Chest radiograph findings usually clear more slowly than clinical manifestations (see "Treatment of community-acquired pneumonia
in adults who require hospitalization", section on 'Radiographic response').
Among patients who have clinical resolution following treatment for CAP, we recommend restricting follow-up chest radiographs to patients >50 years of age; follow-
up chest radiograph is particularly important for males and smokers in this age group. When indicated, we suggest that follow-up chest radiographs be performed 7
to 12 weeks following treatment to document resolution of the pneumonia and exclude underlying diseases, such as malignancy [36]. In contrast, routine chest
radiograph for follow-up of all CAP patients who are responding clinically is unnecessary.

The data to support follow-up chest radiographs in older patients is discussed separately. (See "Treatment of community-acquired pneumonia in adults who require
hospitalization", section on 'Follow-up chest radiograph'.)

The nonresponding patient — General issues relating to nonresolving pneumonia are discussed in detail separately. (See "Nonresolving pneumonia".)

Among patients with CAP, nonresponse is primarily seen in those who require hospitalization, occurring in 6 to 15 percent of such patients. The incidence of
treatment failure is not well defined in ambulatory patients with CAP because population-based studies would be required [2].

VACCINATION — Patients with community-acquired pneumonia should be appropriately vaccinated for influenza and pneumococcal infection. Screening for
influenza vaccination status is warranted during influenza season (eg, from October through March in the northern hemisphere) in all patients. Screening for
pneumococcal vaccination status is warranted in patients age 65 or older or with other indications for vaccination (such as presence of comorbidity or smoking).
Vaccination can be performed during outpatient treatment. (See "Seasonal influenza vaccination in adults" and "Pneumococcal vaccination in adults".)

SMOKING CESSATION — Smoking cessation should be a goal for patients with CAP who smoke [2]. (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 pneumonia in adults".)

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 about a given condition.
These articles are best for patients who want a general overview 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 e-mail 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 topics (see "Patient education: Pneumonia in adults (The Basics)")

● Beyond the Basics topics (see "Patient education: Pneumonia in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Most initial treatment regimens for community-acquired pneumonia (CAP) are empiric. A limited number of pathogens are responsible for the majority of cases
of CAP (table 1). However, local epidemiology, travel history, and other epidemiologic and clinical clues should be considered when selecting an empiric regimen.
Antibiotics should be started as soon as possible once the diagnosis of CAP is established. The presence of an infiltrate on plain chest radiograph is considered
the gold standard for diagnosing pneumonia when clinical (and, in some cases, microbiologic) features are supportive. (See 'Principles of antimicrobial therapy'
above.)

● Emerging drug-resistant Streptococcus pneumoniae complicates the use of empiric treatment. Treatment failures have been demonstrated with use of
macrolides for macrolide-resistant organisms. We recommend not using macrolide monotherapy for patients who have received an antibiotic within the
preceding three months or for patients who reside in regions where the local rate of macrolide resistance is >25 percent (including all regions in the United
States and certain other countries) (Grade 1B). (See 'North America' above.)

● Despite in vitro resistance, penicillin-resistant pneumococci will likely respond to higher-dose beta-lactams other than cefuroxime. (See 'Risk factors for drug
resistance' above.)

● North American and British guidelines differ in their recommendations for first-line therapy for outpatient pneumonia. British guidelines promote amoxicillin and
place less significance on atypical pathogens. North American guidelines from 2007 advocate treating both atypical pathogens and pneumococcus and suggest
macrolides or doxycycline when antibiotic resistance is not anticipated. (See 'Guidelines' above and 'Coverage of atypical pathogens' above.)

● For patients with an established diagnosis of CAP who do not require hospitalization but who have a major comorbidity, a history of recent antibiotic use, or
reside in a region in which both the local overall rate of macrolide resistance among S. pneumoniae (high level and low level) is ≥25 percent (including all
regions of the United States and certain other countries) and the local rate of doxycycline-resistant S. pneumoniae is ≥25 percent, we suggest empiric
combination therapy with a beta-lactam plus either a macrolide or doxycycline or monotherapy with a respiratory fluoroquinolone (algorithm 2) (Grade 2A). If a
beta-lactam combination is used, amoxicillin (1 g three times daily) and amoxicillin-clavulanate XR (2 g twice daily) are the preferred agents; alternatives include
cefpodoxime (200 mg twice daily) and cefuroxime (500 mg twice daily), but in vitro data suggest that they are less active against S. pneumoniae than
amoxicillin. Appropriate fluoroquinolones include levofloxacin 750 mg daily, moxifloxacin 400 mg daily, and gemifloxacin 320 mg daily. For nonpregnant patients
at risk for QT interval prolongation, we favor combination therapy with a beta-lactam plus doxycycline in order to avoid the QT interval-prolonging effects of
fluoroquinolones and macrolides. (See 'Comorbidities or recent antibiotic use' above.)

● For patients with CAP who do not require hospitalization, have no major comorbidities, have not used antibiotics within the last three months, and reside in a
region in which there is not a high prevalence of macrolide-resistant S. pneumoniae (<25 percent), we suggest empiric treatment with an advanced macrolide
(algorithm 2) (Grade 2A). Regimens include azithromycin (500 mg on day 1 followed by four days of 250 mg a day or 500 mg daily for three days), clarithromycin
(500 mg twice daily), or clarithromycin XL (two 500 mg tablets once daily). (See 'No comorbidities, no recent antibiotic use' above.)

● For nonpregnant patients with CAP who do not require hospitalization, have no major comorbidities, and have not used antibiotics within the last three months
but who cannot take a macrolide due to a high local rate (≥25 percent) of macrolide-resistant S. pneumoniae or a contraindication and who live in a region in
which the local rate of doxycycline-resistant S. pneumoniae is <25 percent or is unknown, we suggest doxycycline (100 mg orally twice daily) (algorithm 2)
(Grade 2C). (See 'High rate (≥25 percent) of macrolide resistance (includes United States)' above.)
 ● Most outpatients with CAP should be treated for five days, including those receiving azithromycin 500 mg on the first day followed by 250 mg daily on
subsequent days and those receiving any other antibiotic. Because of its long half-life, patients 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 (table 5). (See 'Treatment duration and response' above.)

● Patients who have not responded to therapy after 48 to 72 hours should be reevaluated. (See "Nonresolving pneumonia".)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 7031 Version 46.0

GRAPHICS

Community-acquired pneumonia: Determining the appropriate site of treatment in adults

ICU: intensive care unit; ED: emergency department; PSI: pneumonia severity index.
* Although a definitive etiologic diagnosis is often not established until after the site of treatment decision has been made, clinical or epidemiologic evidence favoring a pathogen associated with rapidly progressive
pneumonia (eg, post-influenza bacterial pneumonia, severe acute respiratory syndrome, Middle East respiratory syndrome, avian influenza [eg, H5N1, H7N9], Legionella pneumonia) should be considered and, if deemed
likely, warrant hospital admission.
¶ Among the available scoring systems for determining the need for admission in patients with community-acquired pneumonia (CAP), we prefer the PSI because it 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.
Δ 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.
◊ 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.
§ Some PSI class II and III patients may benefit from in-home healthcare support, also termed "hospital-at-home," (eg, a visiting nurse, intravenous fluids, intravenous antibiotics).

Graphic 113076 Version 2.0

Microbial etiology of community-acquired pneumonia by site of care*

Outpatients Ward patients Intensive care unit patients

 
 Spain [1 ] Canada [2] Spain [1] United States [3] Spain [1] United States [3]

Total patients evaluated 514 507 2521 585 488 145

Patients in whom a 161 (31.3) 244 (48.1) 1042 (41) 120 (21) 260 (53) 57 (39)
pathogen was identified

Patients in whom no 353 (68.7) 263 (51.9) 1479 (59) 465 (79) 228 (47) 88 (61)
pathogen was identified

Pathogen ¶

Streptococcus 56 (10.9) 30 (5.9) 447 (17.7) 38 (6.5) 110 (22.5) 22 (15.2)

pneumoniae

Other Streptococcus 0 5 (1.0) 0 0 0 0

spp

Haemophilus influenza 8 (1.6) 25 (4.9) 54 (2.1) 16 (2.7) 8 (1.6) 3 (2.1)

Haemophilus 0 10 (2.0) 0 0 0 0
parainfluenzae

Moraxella cattarrhalis 0 6 (1.2) 4 (0.2) 0 1 (0.2) 0

Legionella pneumophila 10 (1.9) Δ 87 (3.5) ◊ 21 (4.3) ◊

Mycoplasma 27 (5.3) § 87 (17.2) § 32 (1.3) § ¥ 6 (1.2) § ¥

pneumoniae

Chlamydia pneumoniae 10 (1.9) § 72 (14.2) § 32 (1.3) § ¥ 8 (1.6) § ¥

Coxiella burnetii 11 (2.1) § Δ 17 (0.7) § ¥ 2 (0.4) § ¥

Staphylococcus aureus 1 (0.2) 6 (1.2) 18 (0.7) 25 (4.3) 6 (1.2) 12 (8.3)

MSSA 1 (0.2) NR 9 (0.4) 18 (3.1) 4 (0.8) 9 (6.2)

MRSA 0 NR 9 (0.4) 7 (1.2) 2 (0.4) 3 (2.1)

Gram-negative enteric 1 (0.2) 2 (0.4) 23 (0.9) 15 (2.6) 3 (0.6) 4 (2.8)

bacilli

Pseudomonas 1 (0.2) 1 (0.2) 37 (1.5) 12 (2.1) 12 (2.5) 8 (5.5)

aeruginosa

Respiratory viruses ‡ 15 (2.9) § † 123 (4.9) § † 10 (2.0) § †

Other pathogen 6 (1.2) 14 (2.8) 33 (1.3) 8 (1.4) 15 (3.1) 3 (2.1)

>1 pathogen 15 (2.9) ** 135 (5.4) 6 (1.0) 58 (11.9) 7 (4.8)

Diagnostic methods
Cultures (sputum, blood,
transthoracic needle
aspirate, transbronchial
aspirates, BAL fluid,
protected specimen brush
respiratory samples,
pleural fluid), serologic
testing (for M. pneumoniae,
C. pneumoniae, L.
pneumophila, C. burnetti,
influenza A and B,
parainfluenza viruses 1 to
3, respiratory syncytial
virus, adenovirus), urinary
antigen testing (for S.
pneumoniae and L.
pneumophila),
immunofluorescence
assay plus virus isolation
or reverse transcriptase
PCR for influenza A and B,
parainfluenza viruses 1 to
3, respiratory syncytial
virus, adenovirus
Cultures (sputum, blood), Cultures (sputum, blood,
serologic testing (for M. transthoracic needle
pneumoniae, C. aspirate, transbronchial
pneumoniae) aspirates, BAL fluid,
protected specimen brush
respiratory samples,
pleural fluid), serologic
testing (for M. pneumoniae,
C. pneumoniae, L.
pneumophila, C. burnetti,
influenza A and B,
parainfluenza viruses 1 to
3, respiratory syncytial
virus, adenovirus), urinary
antigen testing (for S.
pneumoniae and L.
pneumophila),
immunofluorescence
assay plus virus isolation
or reverse transcriptase
PCR for influenza A and B,
parainfluenza viruses 1 to
3, respiratory syncytial
virus, adenovirus
Cultures (blood,
endotracheal aspirates,
protected specimen brush
respiratory samples, BAL
fluid, pleural fluid), urinary
antigen (for L.
pneumophila)
Cultures (sputum, blood, Cultures (blood,
transthoracic needle endotracheal aspirates,
aspirate, transbronchial protected specimen brush
aspirates, BAL fluid, respiratory samples, BAL
protected specimen brush fluid, pleural fluid), urinary
respiratory samples, antigen testing (for L.
pleural fluid), serologic pneumophila)
testing (for M. pneumoniae,
C. pneumoniae, L.
pneumophila, C. burnetti,
influenza A and B,
parainfluenza viruses 1 to
3, respiratory syncytial
virus, adenovirus), urinary
antigen testing (for S.
pneumoniae and L.
pneumophila),
immunofluorescence
assay plus virus isolation
or reverse transcriptase
PCR for influenza A and B,
parainfluenza viruses 1 to
3, respiratory syncytial
virus, adenovirus

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 percent). Among the 244 patients in whom a pathogen was identified, S. pneumoniae was detected in 12.3 percent.
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.

Graphic 72014 Version 10.0

IDSA/ATS guidelines: Recommended empiric antibiotics for community-acquired pneumonia in adults

Outpatient treatment
1. Previously healthy and no use of antimicrobials within the previous three months:
A macrolide (azithromycin, clarithromycin, or erythromycin)
OR
Doxycyline*

2. Presence of comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppressing conditions or use of immunosuppressing drugs;
or use of antimicrobials within the previous three months (in which case an alternative from a different class should be selected):
A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])
OR
A beta-lactam (first-line agents: high-dose amoxicillin, amoxicillin-clavulanate; alternative agents: ceftriaxone, cefpodoxime, or cefuroxime) PLUS a macrolide (azithromycin, clarithromycin, or erythromycin)*

3. In regions with a high rate (>25 percent) of infection with high-level (MIC ≥16 mcg/mL) macrolide-resistant Streptococcus pneumoniae, consider use of alternative agents listed in (2) above.

Inpatients, non-ICU treatment

A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])
OR
An antipneumococcal beta-lactam (preferred agents: cefotaxime, ceftriaxone, or ampicillin-sulbactam; or ertapenem for selected patients) ¶ PLUS a macrolide (azithromycin, clarithromycin, or
erythromycin)* Δ

Inpatients, ICU treatment

An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS azithromycin
OR
An antipneumococcal beta-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg])
OR
For penicillin-allergic patients, a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]) PLUS aztreonam

Special concerns
If Pseudomonas aeruginosa is a consideration:
An antipneumococcal, antipseudomonal beta-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS either ciprofloxacin or levofloxacin (750 mg)
OR
The above beta-lactam PLUS an aminoglycoside PLUS azithromycin
OR
The above beta-lactam PLUS an aminoglycoside PLUS a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin [750 mg]); for penicillin-allergic patients, substitute aztreonam for above beta-lactam

If CA-MRSA is a consideration:
Add vancomycin or linezolid

This table provides the 2007 recommendations of the Infectious Diseases Society of America and the American Thoracic Society for reference purposes. Refer to the UpToDate text for information
about choosing between the different guidelines and about the preferred doses and durations of the individual antibiotics.

IDSA: Infectious Diseases Society of America; ATS: American Thoracic Society; CAP: community-acquired pneumonia; CA-MRSA: community-acquired methicillin-resistant Staphylococcus aureus; ICU: intensive care
unit; MIC: minimum inhibitory concentration.
* Doxycycline may be used as an alternative to a macrolide, but there is stronger evidence to support the use of a macrolide than doxycycline for CAP.
¶ Ceftaroline can be used as an alternative to these agents. It is a fifth-generation cephalosporin that was not included in the 2007 IDSA/ATS guidelines for the management of CAP since it was not US Food and
Drug Administration (FDA) approved for CAP until 2010. Ceftaroline has a spectrum of activity like that of ceftriaxone, including good in vivo activity against Streptococcus pneumoniae. It is also active against MRSA,
unlike older cephalosporins. However, it is not FDA approved for CAP involving MRSA since patients with MRSA were excluded from the trials. Ceftaroline is more expensive (average wholesale price 82 USD per day)
compared with the alternative agents, which are all off patent. [1]
Δ Monotherapy with tigecycline may be used in patients who cannot take either a beta-lactam or a fluoroquinolone. Tigecycline was not included in the 2007 IDSA/ATS guidelines for the management of CAP
because it was not FDA approved for CAP until 2009. It has been associated with increased mortality, as discussed further in the UpToDate topic review.

Reference:
1. File TM Jr, Low DE, Eckburg PB, et al. Integrated analysis of FOCUS 1 and FOCUS 2: randomized, doubled-blinded, multicenter phase 3 trials of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in
patients with community-acquired pneumonia. Clin Infect Dis 2010; 51:1395.
Modified with permission from: Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired
pneumonia in adults. Clin Infect Dis 2007; 44 Suppl 2:S27. Copyright © 2007 University of Chicago Press.

http://www.journals.uchicago.edu/
Graphic 71665 Version 18.0
British Thoracic Society guidelines: Initial empirical treatment regimens for community-acquired pneumonia in adults

Pneumonia severity (based on clinical judgement

Treatment site Preferred treatment Alternative treatment
supported by CURB65 severity score)

Low severity (eg, CURB65 = 0 to 1 or CRB65 score = 0, <3 Home Amoxicillin 500 mg orally three times daily Doxycycline 200 mg loading dose then 100 mg orally once
percent mortality) daily or clarithromycin 500 mg orally twice daily

Low severity (eg, CURB65 = 0 to 1, <3 percent mortality) but Hospital Amoxicillin 500 mg orally three times daily Doxycycline 200 mg loading dose then 100 mg orally once
admission indicated for reasons other than pneumonia If oral administration not possible: amoxicillin 500 mg IV daily or clarithromycin 500 mg orally twice daily
severity (eg, social reasons/unstable comorbid illness) three times daily*

Moderate severity (eg, CURB65 = 2, 9 percent mortality)
Hospital Amoxicillin 500 mg to 1 gram orally three times daily plus Doxycycline 200 mg loading dose then 100 mg orally or
clarithromycin 500 mg orally twice daily levofloxacin 500 mg orally once daily or moxifloxacin 400
If oral administration not possible: amoxicillin 500 mg IV mg orally once daily ¶
three times daily* or benzylpenicillin (penicillin G) 1.2 grams
IV four times daily plus clarithromycin 500 mg IV twice
daily*

High severity (eg, CURB65 = 3 to 5, 15 to 40 percent Hospital (consider Antibiotics given as soon as possible Benzylpenicillin (penicillin G) 1.2 grams IV four times daily
mortality) critical care Co-amoxiclav (amoxicillin-clavulanate potassium) 1.2 plus either levofloxacin 500 mg IV twice daily or
review) grams IV three times daily* plus clarithromycin 500 mg IV ciprofloxacin 400 mg IV twice daily
twice daily* OR
(If Legionella strongly suspected, consider adding Cefuroxime 1.5 grams IV three times daily or cefotaxime 1
levofloxacin Δ) gram IV three times daily or ceftriaxone 2 grams IV once
daily, plus clarithromycin 500 mg IV twice daily*
(If Legionella strongly suspected, consider adding
levofloxacin Δ)

This table provides the 2009 guideline recommendations of the British Thoracic Society for reference purposes. Refer to the UpToDate text for information about choosing between the different
guidelines and about the preferred doses and durations of the individual antibiotics.

CAP: community-acquired pneumonia; IV: intravenous.

* Intravenous preparation not available in the United States.
¶ Following reports of an increased risk of adverse hepatic reactions associated with oral moxifloxacin, in October 2008 the European Medicines Agency (EMEA) recommended that moxifloxacin "should be used
only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of this infection."
Δ Caution: Risk of QT prolongation with macrolide-quinolone combination.

Reproduced with permission from: Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009; 64 Suppl 3:iii1. Copyright © 2009
BMJ Publishing Group Ltd.

Graphic 74382 Version 12.0

Community-acquired pneumonia: Empiric outpatient antibiotic selection in adults*

* This algorithm is intended for patients in whom outpatient therapy is considered appropriate. Refer to related UpToDate content to determine the
site of care.
¶ Major comorbidities include chronic obstructive pulmonary disease (COPD), liver or renal disease, cancer, diabetes, congestive heart failure,
alcoholism, and immunosuppression.
Δ In some regions of the world, including the United States, southern Europe, and Asia, the overall prevalence of macrolide-resistant S. pneumoniae
(high level and low level) is now >25 percent. In such regions, macrolide monotherapy should not be given.
◊ Examples of contraindications include increased risk for a prolonged QT interval and allergy.
§ Local rates of doxycycline-resistant S. pneumoniae are not readily available to most clinicians, but clinicians may be able to determine the local
rates of resistance by consulting with their local hospital's microbiology laboratory.
¥ Refer to the UpToDate topic review on treatment of community-acquired pneumonia in adults in the outpatient setting for detailed
recommendations regarding antimicrobial regimens. Appropriate macrolides include azithromycin and clarithromycin. Preferred beta-lactams
include amoxicillin and amoxicillin-clavulanate; alternative beta-lactams include cefpodoxime and cefuroxime. Appropriate fluoroquinolones include
levofloxacin, moxifloxacin, and gemifloxacin.
‡ The greater convenience of fluoroquinolone monotherapy must be balanced against the severity of adverse effects (including the risk for
Clostridium difficile infection) and the risk of selection for resistance in colonizing organisms, which are generally thought to be greater with
fluoroquinolones. Refer to the UpToDate topic review on treatment of community-acquired pneumonia in adults in the outpatient setting for
additional details.
† Doxycycline should not be used in pregnant women.

Graphic 111829 Version 3.0

Recommended antimicrobial therapy for specific pathogens causing community-acquired pneumonia in adults

Organism Preferred antimicrobial(s) Alternative antimicrobial(s)

Streptococcus pneumoniae
Penicillin nonresistant; MIC <2 microgram/mL
Penicillin resistant; MIC ≥2 microgram/mL
Penicillin G, amoxicillin Macrolide, cephalosporins (oral [cefpodoxime, cefprozil, cefuroxime,
cefdinir, cefditoren] or parenteral [cefuroxime, ceftriaxone, cefotaxime]),
clindamycin, doxycyline, respiratory fluoroquinolone*
Agents chosen on the basis of susceptibility, including cefotaxime, Vancomycin, linezolid, high-dose amoxicillin (3 g/day with penicillin MIC ≤4
ceftriaxone, fluoroquinolone microgram/mL)

Haemophilus influenzae
Non-beta-lactamase producing Amoxicillin Fluoroquinolone, doxycycline, azithromycin, clarithromycin ¶
Beta-lactamase producing Second- or third-generation cephalosporin, amoxicillin-clavulanate Fluoroquinolone, doxycycline, azithromycin, clarithromycin ¶

Mycoplasma pneumoniae/Chlamydophila pneumoniae Macrolide, a tetracycline Fluoroquinolone

Legionella species Fluoroquinolone, azithromycin Doxycyline

Chlamydophila psittaci A tetracycline Macrolide

Coxiella burnetii A tetracycline Macrolide

Francisella tularensis Doxycycline Gentamicin, streptomycin

Yersinia pestis Streptomycin, gentamicin Doxycyline, fluoroquinolone

Bacillus anthracis (inhalation) Ciprofloxacin, levofloxacin, doxycycline (usually with second agent) Other fluoroquinolones; beta-lactam, if susceptible; rifampin;
clindamycin; chloramphenicol

Enterobacteriaceae Third-generation cephalosporin, carbapenem Δ (drug of choice if Beta-lactam/beta-lactamase inhibitor ◊, fluoroquinolone

extended-spectrum beta-lactamase producer)

Pseudomonas aeruginosa Antipseudomonal beta-lactam § plus (ciprofloxacin or Aminoglycoside plus (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 inhibitor ◊, clindamycin Carbapenem

Influenza virus Refer to associated topic reviews †  

Mycobacterium tuberculosis Isoniazid plus rifampin plus ethambutol plus pyrazinamide Depends on susceptibility pattern. Refer to associated topic
reviews.

Coccidioides species For uncomplicated infection in a normal host, no therapy generally Amphotericin B
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.
* 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).
¶ Azithromycin is more active in vitro than clarithromycin for H. influenzae.
Δ Imipenem-cilastatin, meropenem, ertapenem.
◊ Piperacillin-tazobactam for gram-negative bacilli, ticarcillin-clavulanate, ampicillin-sulbactam, or amoxicillin-clavulanate.
§ Ticarcillin, piperacillin, ceftazidime, cefepime, aztreonam, imipenem, meropenem.
¥ 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.

Graphic 64816 Version 9.0

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.

Graphic 74599 Version 2.0