ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

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

Treatment of community-acquired pneumonia in adults in the outpatient setting
Literature review current through: Sep 2023.
This topic last updated: Apr 15, 2022.

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".)

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

(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 in nursing homes" 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. 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). (Related Pathway(s): Community-acquired pneumonia: Empiric antibiotic selection for adults in the outpatient setting.)

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 Lexicomp drug interactions tool 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. 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, lincosamides, and ketolides" 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 Lexicomp drug interactions tool 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. 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 4). 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 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 5) [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 CAPM. 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 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 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 specific regimen depends on patient age, the presence of comorbidities (ie, chronic pulmonary, liver, heart, or renal disease, cancer, diabetes mellitus, heart failure, alcohol use disorder), smokers, or those who have used antibiotics within the prior three months (algorithm 2).

For otherwise healthy outpatients aged <65 years who have not recently used antibiotics, 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 extended-release amoxicillin-clavulanate (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 − Combination therapy with a third-generation cephalosporin (eg, cefpodoxime) plus a macrolide or doxycycline is our preferred alternative for patients who cannot use penicillins. In general, patients with mild non-immunoglobulin (Ig)E-mediated reactions (eg, maculopapular rash) to penicillin or known cephalosporin tolerance can generally use later-generation cephalosporins safely. Patients with more severe penicillin hypersensitivity reactions should generally avoid empiric treatment with beta-lactams. (See 'Preferred agents' above.)

Differences from ATS/IDSA – Our approach is generally similar to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines with few exceptions:

The ATS/IDSA recommends amoxicillin alone for otherwise healthy outpatients aged <65 years who have not recently used antibiotics; monotherapy with either a macrolide or doxycycline is recommended for those who cannot use penicillins, provided local resistance rates among S. pneumoniae isolates are <25 percent. Our empiric approach is to use amoxicillin plus therapy for atypical pathogens. (See 'Healthy, age <65 years, no recent antibiotic use' above.).

For outpatients who are ≥65 years, smoke, have comorbidities, or have recently used antibiotics, 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. (See 'Comorbidities, age 65 years or older, or recent antibiotic use' above.)

Fluoroquinolones and other alternative agents − Fluoroquinolone monotherapy is equally effective as the above regimens; however, because of its adverse effect profile and potential for promoting drug resistance, we reserve use for patients who cannot tolerate the above regimens. Lefamulin and omadacycline are a 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 are limited; warnings and contraindications exist. (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. Patients who have not responded to therapy after 48 to 72 hours should be re-evaluated. (See 'Duration of therapy' above and 'Follow-up care' above.)

Modifications to empiric regimens − 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). In particular, during influenza season, patients at high risk for poor outcomes from influenza typically warrant antiviral therapy. (See "Seasonal influenza in nonpregnant adults: Treatment".)

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.

  1. File TM. Community-acquired pneumonia. Lancet 2003; 362:1991.
  2. Wunderink RG, Waterer GW. Clinical practice. Community-acquired pneumonia. N Engl J Med 2014; 370:543.
  3. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med 2014; 371:1619.
  4. 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.
  5. American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388.
  6. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016; 63:e61.
  7. Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis 2014; 58:330.
  8. Gross AE, Van Schooneveld TC, Olsen KM, et al. Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia. Antimicrob Agents Chemother 2014; 58:5262.
  9. Yap V, Datta D, Metersky ML. Is the present definition of health care-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens? Infect Dis Clin North Am 2013; 27:1.
  10. 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.
  11. Shorr AF, Zilberberg MD, Reichley R, et al. Validation of a clinical score for assessing the risk of resistant pathogens in patients with pneumonia presenting to the emergency department. Clin Infect Dis 2012; 54:193.
  12. Webb BJ, Dascomb K, Stenehjem E, et al. Derivation and Multicenter Validation of the Drug Resistance in Pneumonia Clinical Prediction Score. Antimicrob Agents Chemother 2016; 60:2652.
  13. Malcolm C, Marrie TJ. Antibiotic therapy for ambulatory patients with community-acquired pneumonia in an emergency department setting. Arch Intern Med 2003; 163:797.
  14. File TM Jr, Marrie TJ. Does empiric therapy for atypical pathogens improve outcomes for patients with CAP? Infect Dis Clin North Am 2013; 27:99.
  15. File TM Jr, Eckburg PB, Talbot GH, et al. Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point. Int J Antimicrob Agents 2017; 50:247.
  16. Pakhale S, Mulpuru S, Verheij TJ, et al. Antibiotics for community-acquired pneumonia in adult outpatients. Cochrane Database Syst Rev 2014; :CD002109.
  17. File TM, Goldberg L, Das A, et al. Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis 2019; 69:1856.
  18. Alexander E, Goldberg L, Das AF, et al. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial. JAMA 2019; 322:1661.
  19. Postma DF, van Werkhoven CH, van Elden LJ, et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med 2015; 372:1312.
  20. Eliakim-Raz N, Robenshtok E, Shefet D, et al. Empiric antibiotic coverage of atypical pathogens for community-acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev 2012; :CD004418.
  21. Garin N, Genné D, Carballo S, et al. β-Lactam monotherapy vs β-lactam-macrolide combination treatment in moderately severe community-acquired pneumonia: a randomized noninferiority trial. JAMA Intern Med 2014; 174:1894.
  22. Kuster SP, Rudnick W, Shigayeva A, et al. Previous antibiotic exposure and antimicrobial resistance in invasive pneumococcal disease: results from prospective surveillance. Clin Infect Dis 2014; 59:944.
  23. Metersky ML, Ma A, Houck PM, Bratzler DW. Antibiotics for bacteremic pneumonia: Improved outcomes with macrolides but not fluoroquinolones. Chest 2007; 131:466.
  24. Martínez JA, Horcajada JP, Almela M, et al. Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia. Clin Infect Dis 2003; 36:389.
  25. Restrepo MI, Mortensen EM, Waterer GW, et al. Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia. Eur Respir J 2009; 33:153.
  26. Martin-Loeches I, Lisboa T, Rodriguez A, et al. Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med 2010; 36:612.
  27. Asadi L, Sligl WI, Eurich DT, et al. Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis. Clin Infect Dis 2012; 55:371.
  28. Raz-Pasteur A, Shasha D, Paul M. Fluoroquinolones or macrolides alone versus combined with β-lactams for adults with community-acquired pneumonia: Systematic review and meta-analysis. Int J Antimicrob Agents 2015; 46:242.
  29. Lee JS, Giesler DL, Gellad WF, Fine MJ. Antibiotic Therapy for Adults Hospitalized With Community-Acquired Pneumonia: A Systematic Review. JAMA 2016; 315:593.
  30. Chalmers JD, Al-Khairalla M, Short PM, et al. Proposed changes to management of lower respiratory tract infections in response to the Clostridium difficile epidemic. J Antimicrob Chemother 2010; 65:608.
  31. Li JZ, Winston LG, Moore DH, Bent S. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med 2007; 120:783.
  32. Dimopoulos G, Matthaiou DK, Karageorgopoulos DE, et al. Short- versus long-course antibacterial therapy for community-acquired pneumonia : a meta-analysis. Drugs 2008; 68:1841.
  33. Tansarli GS, Mylonakis E. Systematic Review and Meta-analysis of the Efficacy of Short-Course Antibiotic Treatments for Community-Acquired Pneumonia in Adults. Antimicrob Agents Chemother 2018; 62.
  34. López-Alcalde J, Rodriguez-Barrientos R, Redondo-Sánchez J, et al. Short-course versus long-course therapy of the same antibiotic for community-acquired pneumonia in adolescent and adult outpatients. Cochrane Database Syst Rev 2018; 9:CD009070.
  35. Metlay JP, Atlas SJ, Borowsky LH, Singer DE. Time course of symptom resolution in patients with community-acquired pneumonia. Respir Med 1998; 92:1137.
  36. 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.
  37. 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.
  38. Bruns AH, Oosterheert JJ, Prokop M, et al. Patterns of resolution of chest radiograph abnormalities in adults hospitalized with severe community-acquired pneumonia. Clin Infect Dis 2007; 45:983.
  39. Mittl RL Jr, Schwab RJ, Duchin JS, et al. Radiographic resolution of community-acquired pneumonia. Am J Respir Crit Care Med 1994; 149:630.
  40. El Solh AA, Aquilina AT, Gunen H, Ramadan F. Radiographic resolution of community-acquired bacterial pneumonia in the elderly. J Am Geriatr Soc 2004; 52:224.
  41. Almirall J, Bolíbar I, Vidal J, et al. Epidemiology of community-acquired pneumonia in adults: a population-based study. Eur Respir J 2000; 15:757.
  42. Arancibia F, Ewig S, Martinez JA, et al. Antimicrobial treatment failures in patients with community-acquired pneumonia: causes and prognostic implications. Am J Respir Crit Care Med 2000; 162:154.
Topic 7031 Version 70.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟