Community-Acquired Pneumonia (CAP)

Practice Essentials

Community-acquired pneumonia (CAP) is one of the most common infectious diseases and is an important cause of mortality and morbidity worldwide. Typical bacterial pathogens that cause CAP include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis (see images below). However, with the advent of novel diagnostic technologies, viral respiratory pathogens are increasingly being identified as frequent etiologies of CAP. The most common viral pathogens recovered from hospitalized patients admitted with CAP include human rhinovirus and influenza.^[1]

View Image

Gram stain showing Streptococcus pneumoniae.

View Image

Gram stain showing Haemophilus influenzae.

Presentation and pathogens in typical community-acquired pneumonia

The term “typical” CAP refers to a bacterial pneumonia caused by pathogens such as S pneumoniae, H influenzae, and M catarrhalis. Patients with typical CAP classically present with fever, a productive cough with purulent sputum, dyspnea, and pleuritic chest pain. Characteristic pulmonary findings on physical examination include the following:

• Tachypnea
• Rales heard over the involved lobe or segment
• Increased tactile fremitus, bronchial breath sounds, and egophony may be present if consolidation has occurred.
• Decreased tactile fremitus and dullness on chest percussion may result from parapneumonic effusion or empyema.

Epidemiologic data may provide clues to the specific pathogen causing CAP, as follows:

• The most common bacterial pathogen overall is S pneumoniae, although, in some settings, including in the United States, its incidence is decreasing, possibly owing to vaccination.^[1]
• Underlying chronic obstructive pulmonary disease (COPD)^[2] : H influenzae or M catarrhalis
• Recent influenza infection^[3] : Staphylococcus aureus or S pneumoniae^[4]
• Alcoholic patient presenting with “currant jelly” sputum: Klebsiella pneumoniae^[2]

Atypical community-acquired pneumonia

The clinical presentation of so-called “atypical” CAP is often subacute and frequently indolent. In addition, patients with atypical CAP may present with more subtle pulmonary findings, nonlobar infiltrates on radiography, and various extrapulmonary manifestations (eg, diarrhea, otalgia). Atypical CAP pathogens include the following:

• Mycoplasmapneumoniae
• Chlamydophila (Chlamydia) pneumoniae
• Legionella pneumophila (Legionnaires disease)
• Respiratory viruses, including the following:
• Influenza A and B
• Rhinovirus
• Respiratory syncytial virus
• Human metapneumovirus
• Adenovirus 4 and 7
• Parainfluenza virus
• • Viruses
    • Coxsackievirus
    • Echovirus
    • Coronavirus (MERS-CoV, SARS)
    • Hantavirus
    • Epstein-Barr virus
    • Cytomegalovirus
    • Herpes simplex virus
    • Human herpesvirus 6
    • Varicella-zoster virus
    • Metapneumovirus^[5]
  • Bacteria
    • Chlamydophila psittaci (psittacosis)
    • Coxiella burnetii (Q fever)
    • Francisella tularensis (tularemia)
  • Mycobacteria
    • Mycobacteria tuberculosis
    • Nontuberculous mycobacteria (uncommon)
  • Endemic fungi (causing subacute or chronic pneumonia)
    • Histoplasma capsulatum
    • Cryptococcus neoformans neoformans and neoformans gattii
    • Coccidioides immitis

   

  

   

Extrapulmonary signs and symptoms seen in some forms of atypical CAP may include the following:

• Mental confusion
• Prominent headaches
• Myalgias
• Ear pain
• Abdominal pain
• Diarrhea
• Rash (Horder spots in psittacosis; erythema multiforme in Mycoplasma pneumonia)
• Nonexudative pharyngitis
• Hemoptysis
• Splenomegaly
• Relative bradycardia

While historical clues and physical examination findings may suggest a causative pathogen, the clinical signs and symptoms of CAP are not sufficiently specific to reliably differentiate the exact etiologic agent.^[6] Therefore, additional testing remains necessary to identify the pathogen and to optimize therapy in CAP.

Workup

Standard diagnostic studies for CAP include the following:

• Chest radiography
• Complete blood cell (CBC) count with differential
• Serum blood urea nitrogen (BUN) and creatinine levels

For patients with severe CAP, patients being empirically treated for methicillin-resistant S aureus (MRSA) or Pseudomonas, or patients in whom a specific etiology is suspected, additional workup may be warranted, including the following:^[7]

• Sputum Gram stain and/or culture
• Blood cultures
• Serum sodium level
• Serum transaminase levels
• Lactic acid level
• C-reactive protein (CRP)
• Lactate dehydrogenase (LDH)
• Molecular diagnostics, ie, polymerase chain reaction (PCR) testing
• Urinary antigen testing for Legionella species

In special situations:

• During influenza season, molecular assay for influenza
• Serologic studies for M pneumoniae, C pneumoniae, Bordetella pertussis, C burnetii
• Creatine phosphokinase (CPK)
• Serum phosphorus level

Chest radiography

Obtain chest radiographs in all patients with suspected CAP to evaluate for an infiltrate and to help exclude conditions that may mimic CAP (ie, lung cancer, pulmonary emboli).^{[8, 9]} Patients who present very early with CAP may have negative findings on chest radiography. In these patients, repeat chest radiography within 24 hours may be beneficial. CT scanning may also be necessary in immunocompromised patients who present with symptoms that suggest CAP or ambiguous symptoms in whom chest radiography findings are negative. Serial chest radiography may be used to observe the progression of CAP; however, radiographic improvement often lags behind clinical improvement.

Hospital admission

Multiple scoring systems are available to assess the severity of CAP and to assist in deciding whether a patient should be hospitalized or admitted to the intensive care unit (ICU). Severe pneumonia is defined as having 1 major or 3 minor criteria. Major criteria include septic shock requiring vasopressors or respiratory failure requiring mechanical ventilation. Minor criteria include the following:^[7]

• Respiratory rate of 30 or more breaths per minute
• PaO₂/FIO₂ ratio of 250 or less
• Multilobar infiltrates
• Confusion
• Uremia
• Leukopenia (WBC < 4000 cells/µl)
• Thrombocytopenia (platelet count < 100,000/µl)
• Hypothermia
• Hypotension

The Pneumonia Severity Index (PSI) is preferred over the CURB-65 (confusion, uremia, respiratory rate, low blood pressure, age >65 years) for determining outpatient versus inpatient treatment. Patients with PSI class IV-V may need hospitalization or more intensive in-home services. ICU admission is recommended for any patient who requires mechanical ventilation or vasopressors. Admission to higher-acuity care or critical care should also be considered in patients with 3 or more minor risk factors for severe pneumonia.

Other scoring systems may also be helpful in certain populations to predict the severity of CAP. The SMART-COP score emphasizes the ability to predict the need for ventilator or vasopressor support and includes systolic blood pressure, multilobar infiltrates, serum albumin levels, respiratory rate, tachycardia, confusion, oxygenation, and pH level. The A-DROP (age, dehydration, respiratory failure, orientation, systolic blood pressure) is also a severity score. Recently, an expanded CURB-65 has been shown to improve prediction of 30-day mortality. It includes LDH, thrombocytopenia, and serum albumin, along with the traditional CURB-65, and has been shown to have better prediction accuracy. The value of adding biomarkers in addition to the above scoring systems to identify patients at risk of worse outcomes is being studied.^{[10, 11, 12, 13, 14]}

More recent research indicates that the use of biomarkers, specifically procalcitonin and CRP, may further increase the ability to identify patients at increased risk for worse outcomes, although this remains controversial. A positive pneumococcal urine antigen result has been associated with a good prognosis.^[15] Certain prior pulmonary pathology, such as past infection with pulmonary tuberculosis, may increase the risk of mortality.^[16]

Antibiotic Therapy

Adequate empiric antimicrobial therapy for CAP includes coverage for S pneumoniae and atypical bacterial pathogens. Outpatient treatment for CAP in patients with no comorbidities and no risk factors for drug-resistant S pneumoniae frequently includes the following:^[7]

• Amoxicillin 1 g PO three times a day OR
• A macrolide (azithromycin 500 mg once and then 250 mg daily, clarithromycin 500 mg twice daily) OR
• Doxycycline 100 mg twice daily

Macrolides should be used only in areas where pneumococcal resistance is less than 25%. During influenza season, it is also reasonable to initiate oseltamivir, zanamivir, or baloxavir therapy in outpatients who present with a flulike illness and pneumonia.

Treatment options for CAP in patients with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia; immunosuppression; prior antibiotics within 90 days; or other risk factors for drug-resistant infection include the following:

• Beta-lactam (high-dose amoxicillin 1 g 3 times/day, amoxicillin/clavulanate 2 g/125 mg twice daily or 500 mg/125 mg three times daily or 875 mg/125 mg twice daily, cefpodoxime 200 mg twice daily, or cefuroxime 500 mg twice daily) plus a macrolide or doxycyclineOR
• Respiratory fluoroquinolones (moxifloxacin 400 mg daily, levofloxacin 750 mg daily)

For hospitalized patients, therapy consists of the following:

• Beta-lactams (ampicillin/sulbactam 1.5-3 g every 6 hours, ceftriaxone 1-2 g daily, cefotaxime 1-2 g every 8 hours, or ceftaroline 600 mg every 12 hours) plus a macrolide OR
• Respiratory fluoroquinolone OR
• If macrolides and fluoroquinolones are contraindicated: Beta-lactam as above plus doxycycline

Therapy in ICU patients includes the following:

• Beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) plus either a macrolide or respiratory fluoroquinolone
• For patients with penicillin allergy, a respiratory fluoroquinolone and aztreonam

Risk factors for Pseudomonas pneumonia include structural lung disease, COPD, and bronchiectasis^[4] If Pseudomonas is suspected, therapy consists of an anti-pneumococcal and anti-pseudomonal beta-lactam (piperacillin/tazobactam 4.5 g every 6 hours, cefepime 2 g every 8 hours, ceftazidime 2 g every 8 hours, aztreonam 2 g every 8 hours, meropenem 1 g every 8 hours, or imipenem 500 mg every 6 hours).^[7]

In patients with severe penicillin allergy, aztreonam may be used instead of the beta-lactam in the regimen listed above. It is worth noting that many reported penicillin allergies are not true allergies. Owing to the limited spectrum of aztreonam and the relatively low likelihood of penicillin allergy cross-reacting with cephalosporins (2%), cefepime is a reasonable choice after considering the balance of benefit and risk.^[17]

Doripenem is no longer recommended for ventilator-acquired pneumonia (VAP) and is not FDA-approved for treating any kind of pneumonia.^[18]

If methicillin-resistant S aureus (MRSA) is suspected, vancomycin 15 mg/kg every 12 hours adjusted based on levels or linezolid 600 mg every 12 hours should be added. Risk factors for MRSA include hemoptysis, recent influenza, neutropenia, hemodialysis, and congestive heart failure.^[4] During influenza season, it is also reasonable to start oseltamivir, zanamivir, peramivir, or baloxavir therapy to treat influenza in patients with MRSA CAP, as well as in patients who present with a flulike illness and pneumonia, as influenza may have preceded the MRSA infection.

Rapid initiation of therapy is important for improved outcomes in CAP, although blanket measures to hasten treatment are not without potential negative consequences. Quality-improvement efforts aimed at the administration of antibiotics within a certain time period have contributed to increased inappropriate antibiotic use and increased incidence of Clostridium difficile colitis. Nevertheless, in patients with signs of severe CAP or sepsis, antibiotics should be given within the first hour of hypotension onset to reduce mortality.^[19] At minimum, blood cultures and, ideally, sputum cultures should be collected prior to the first antibiotic dose, although antibiotics should not be delayed. Results of respiratory specimen cultures, blood cultures, and pleural fluid analysis; PCR of respiratory samples; or antigen tests should be monitored and used to target therapy whenever possible. Inpatient CAP therapy usually consists of intravenous antibiotics followed by transition to an oral course of therapy.^{[20, 21, 22, 23]} Patients who are severely ill or who are unable to tolerate or absorb oral medications may require a longer duration of parenteral therapy before switching to an oral antibiotic.^[24]

Mild to moderately ill patients with CAP may be treated entirely via the oral route, on either an inpatient or outpatient basis. The duration of therapy for uncomplicated CAP is usually 5 days.^{[25, 19]} The duration of therapy for CAP due to suspected or proven Pseudomonas or MRSA should be 7 days. Patients should be afebrile for 48-72 hours and have no signs of instability before antibiotic therapy is stopped. The duration of therapy may need to be increased if the initial empiric therapy has no activity against the specific pathogen or if the pneumonia is complicated by extrapulmonary infection.^[7] Immunocompromised hosts who present with CAP are treated in a manner similar to that of otherwise healthy hosts but may require a longer duration of therapy. Additional investigations into pathogens associated with compromised hosts may also need to be pursued.

• References

Overview

Community-acquired pneumonia (CAP) is one of the most common infectious diseases addressed by clinicians and is an important cause of mortality and morbidity worldwide.

Typical bacterial pathogens that cause CAP include S pneumoniae, H influenzae, and M catarrhalis. Numerous other organisms can cause CAP in the appropriate clinical setting. Furthermore, the so-called “atypical CAP” pathogens are actually common causes of CAP and were originally classified as atypical because they are not readily detectable on Gram stain or cultivatable on standard bacteriologic media.

CAP is usually acquired via inhalation or aspiration of a pathogenic organism.

Aspiration pneumonia is commonly caused by multiple pathogens (eg, aerobic/anaerobic oral organisms).

Severe community-acquired pneumonia

Severe CAP frequently develops in individuals with comorbid factors such as underlying cardiopulmonary disease, diminished splenic function, and/or heightened pathogenic virulence. Even in young and/or healthy hosts, severe CAP can develop if the causative pathogen is sufficiently virulent. For example, influenza, severe acute respiratory syndrome (SARS), Hantavirus pulmonary syndrome (HPS), and Legionnaires disease may present as severe CAP.^{[26, 27, 28, 29]}

Patients with severe CAP should have the benefit of an infectious disease specialist to assist in identifying and optimally managing the underlying cause.

Complications associated with community-acquired pneumonia

The risk of complications in CAP depend on the infecting pathogen and the patient’s baseline health. For example, various organisms can cause empyema, including S pneumoniae, K pneumoniae (classically occurring in patients with chronic alcoholism), group A Streptococcus, and S aureus. Cavitation is not a typical feature of pneumococcal pneumonia but is relatively common in K pneumoniae infections.

Cardiovascular complications, including acute myocardial infarction or congestive heart failure (CHF), may be precipitated by CAP in up to one third of patients.^{[30, 31, 32]} A 2019 post-hoc analysis of a cluster-randomized controlled trial indicated increased rates of hospital-acquired cardiac events, mostly heart failure, after erythromycin use.^[33]

Patients with CAP who have impaired splenic function may develop overwhelming pneumococcal sepsis, potentially leading to death within 12-24 hours, regardless of the antimicrobial regimen used.

Morbidity and mortality

Morbidity and mortality associated with CAP are most common in elderly patients and immunocompromised hosts.

Other factors that may portend an increased risk of morbidity and mortality in individuals with CAP include significant comorbidities such as structural lung disease or cancer and presenting signs of severe infection such as an increased respiratory rate, hypotension, fever, multilobar involvement, anemia, and hypoxia.^[34] An elevated procalcitonin level may also be associated with an increased mortality risk, although the specific threshold for increased risk remains to be determined.^[12]

For more information, see the following:

• Mycoplasma Pneumonia
• Bacterial Pneumonia
• Viral Pneumonia
• Pneumocystis Jiroveci (Carinii) Pneumonia Imaging
• Aspiration Pneumonia
• Nosocomial Pneumonia
• Ventilator-Associated Pneumonia
• Pneumocystis (carinii) jiroveci Pneumonia
• Fungal Pneumonia
• Immunocompromised Pneumonia
• Nursing Home Acquired Pneumonia
• Chlamydial Pneumonia
• Lymphocytic Interstitial Pneumonia
• Imaging Typical Bacterial Pneumonia
• Imaging Atypical Bacterial Pneumonia
• Imaging Viral Pneumonia

• References

Etiology of Community-Acquired Pneumonia

The definitive microbiologic etiology is determined in less than half of patients who develop community-acquired pneumonia (CAP); the exact rate depends on the patient population and diagnostic testing used.^{[1, 35, 36]} Organisms have been traditionally classified as “typical” or “atypical” CAP pathogens depending on their ability to be detected on Gram stain or standard bacterial cultures.

Typical community-acquired pneumonia pathogens

Typical bacterial pathogens that cause CAP include S pneumoniae, H influenza, and M catarrhalis (Gram stains shown below). The frequency with which CAP is attributable to one of these pathogens varies according to epidemiologic factors (eg, seasonality, patient demographics, exposure history) and the diagnostic testing used. In the past, these organisms had been reported to account for most CAP cases.^[37] However, with improvement in diagnostic techniques allowing for better identification of viruses and fastidious bacteria, our understanding of the etiologic agents involved in the development of CAP has evolved. As a result, a smaller percentage of CAP cases are now being attributed to these typical bacterial pathogens. In addition, the possibility of polymicrobial infections has received increased awareness; in recent epidemiologic studies, two pathogens, typically a virus and bacteria combination, were identified in over 30% of cases.^{[1, 35, 5]}

View Image

Gram stain showing Streptococcus pneumoniae.

View Image

Gram stain showing Haemophilus influenzae.

S pneumoniae remains the most common bacterial agent responsible for CAP. The incidence of S pneumoniae pneumonia varies according to the population studied. A 2015 study of 267 patients with CAP in Norway reported that S pneumoniae accounted for 30% of cases; this represented 48.5% of the cases in which an organism was identified.^[35] A separate study of adults with CAP in the United States identified S pneumoniae as the etiologic agent in only 5% of total cases of CAP (13.5% of cases with an identified pathogen).^[1] Declining tobacco smoking and widespread pneumococcal vaccination have been postulated as potential contributors to the decreased rates of S pneumoniae infection in the United States.^[36]

S aureus has not traditionally been considered a typical cause of CAP in otherwise healthy hosts, with the exception of potentially severe CAP after influenza infection.^[3] Community-acquired methicillin-resistant S aureus (MRSA) has been associated with multilobar necrotizing CAP, including in previously healthy individuals. However, in a prospective multicenter US surveillance study of 2259 adults hospitalized for CAP, S aureus was identified in only 1.6% of patients, and MRSA accounted for only 0.7% of all cases.^[38] Interestingly, in that study, the clinical presentation of MRSA CAP did not differ from that of all-cause non–S aureus or pneumococcal CAP with regard to concurrent influenza infection, presence of multilobar infiltrates, or hemoptysis. MRSA CAP was significantly associated with prior long-term hemodialysis use and carried a higher inpatient mortality rate (13.3%) than all-cause non–S aureus CAP (2%).^[38]

Importantly, K pneumoniae and Pseudomonas aeruginosa are not typical causes of CAP in otherwise healthy hosts. K pneumoniae CAP occurs primarily in individuals with chronic alcoholism or diabetes mellitus. P aeruginosa is a cause of CAP in patients with underlying lung disease such as bronchiectasis or cystic fibrosis.

In certain patients admitted to the ICU, the microbial etiology of pneumonia may be complex. In a study by Cilloniz et al, 11% of cases were polymicrobial. The most frequently identified pathogens in polymicrobial infections were S pneumoniae, respiratory viruses, and P aeruginosa. Chronic respiratory disease and acute respiratory distress syndrome (ARDS) criteria were independent predictors of a polymicrobial infection.^[39] Bacterial and viral co-infection may portend a worse prognosis.^{[40, 41]}

Other gram-negative pathogens (eg, Enterobacter species, Serratia species, Stenotrophomonas maltophilia, Burkholderia cepacia) rarely cause CAP in patients without underlying lung disease or immunosuppression.

Atypical community-acquired pneumonia pathogens

Atypical bacterial pneumonias can be differentiated into those caused by zoonotic or nonzoonotic atypical pathogens.

Zoonotic atypical CAP pathogens include Chlamydophila (Chlamydia) psittaci (psittacosis), F tularensis (tularemia), and C burnetii (Q fever).

Nonzoonotic atypical CAP pathogens include Legionella species (Legionnaires disease), M pneumoniae, and C pneumoniae.^[42]

Respiratory viruses are another important cause of atypical CAP. While certain viruses may be zoonotically transmitted (eg, Hantavirus and avian influenza), most are transmitted person-to-person.

• References

Epidemiology of Community-Acquired Pneumonia

The incidence of CAP varies greatly from country to country. In the United States, CAP is estimated to occur in 248 of 10,000 adults. Other countries report different frequencies, such as 8.1 per 10,000 in Vietnam and 31.2 per 10,000 in the United Kingdom. Rates also vary based on the population studied. In adults older than 65 years, 130.5 per 10,000 develop CAP in Malaysia, whereas 76.5 per 10,000 develop CAP in Germany. In individuals aged 85 years or older in Norway, the incidence of CAP is 172.4 per 10,000.^[5] Influenza and pneumonia combined remain in the top 10 leading causes of death in the United States, ranking 8 of 10 in 2015. The combination was responsible for 2% (57,062) of deaths in 2015, an increase of 3.3% from 2014.^[43] In addition, survivors of CAP have an increased incidence of cardiovascular events and mortality risk for months to years after CAP. As many as 20% of CAP survivors have been shown to have cardiovascular events, and mortality is up to 30% 2-5 years after CAP.^[5]

The cost of CAP has been examined in numerous studies. In a 2018 retrospective analysis of claims data for adults aged 65 years or older in a Medicare insurance plan, the rate of CAP was 846.7 per 100,000 person-years, which was greater than rates for myocardial infarction (405), stroke (278.9), and osteoporotic fractures (343.9). This study noted vaccinations against influenza and Pneumococcus infection cost $40 million; however, prevention for stroke and myocardial infarction cost more than $661 million.^[44]

Age

Advanced age is associated not only with a higher incidence of CAP but also with more severe disease, greater need for hospitalization, and higher mortality.^{[25, 45]}

CAP encountered in the ambulatory setting is more common among young adults and is usually due to so-called atypical CAP pathogens (eg, Mycoplasma pneumoniae).^[46]

• References

Prognosis of Community-Acquired Pneumonia

Negative prognostic factors in community-acquired pneumonia (CAP) include preexisting lung disease, underlying cardiac disease, poor splenic function, advanced age, multilobar involvement, past infection with tuberculosis, and delayed initiation of appropriate antimicrobial therapy.^{[47, 16]}

• References

Extrapulmonary Findings in Atypical Community-Acquired Pneumonia

Atypical community-acquired pneumonia (CAP) has classically been associated with more extrapulmonary manifestations than typical bacterial CAP. However, there can be considerable overlap in the clinical presentation of CAP due to various pathogens such that a definitive microbiologic diagnosis cannot be made based on signs and symptoms alone. Certain constellations of findings in the setting of appropriate historical clues may suggest an increased likelihood of a specific pathogen, thus warranting a targeted investigation for that organism. A detailed review of all potential extrapulmonary findings in CAP is beyond the scope of this article; however, some classic associations are included below:

M pneumoniae CAP is associated with the following findings:^[48]

• Headache, fever, malaise, sore throat in young adult with insidious onset of cough
• Erythema multiforme major (Stevens-Johnson syndrome)
• Cardiac conduction abnormalities
• Hemolytic anemia and cold-agglutinin syndrome
• Neurologic abnormalities, including aseptic meningitis or meningoencephalitis, Guillain-Barre syndrome, transverse myelitis
• Epidemic outbreaks, eg, in schools or military barracks

Legionella pneumophila CAP (Legionnaires disease) is associated with the following findings:^[49]

• Gastrointestinal and neurologic symptoms in the setting of pneumonia
• Positive history of water or travel exposure
• Relative bradycardia during febrile episode
• Hyponatremia, hypophosphatemia, elevated creatine phosphokinase (CPK) level, elevated ferritin level, myoglobinuria
• Leukocytosis with relative lymphopenia
• Unresponsive to beta-lactam antibiotics

View Image

A case of Legionnaires disease from the Philadelphia outbreak, showing characteristics of relative bradycardia and extrapulmonary involvement.

View Image

This graph outlines a case of Legionella pneumonia, showing characteristics of bradycardia and extrapulmonary involvement. Also shown is an initial la....

C burnetii CAP (Q fever) is associated with the following factors:^{[50, 51]}

• Acute infection
• Severe retrobulbar headache, myalgias, fever, rigors, nonproductive cough
• Elevated levels of transaminases and thrombocytopenia
• Maculopapular or purpuric rash
• Zoonotic exposure (goats, sheep, cattle most common)

Community-acquired pneumonia and shock

With the exception of CAP due to particularly virulent organisms (eg, S aureus, Hantavirus, severe acute respiratory syndrome [SARS], Legionella), CAP does not typically present with shock in otherwise healthy hosts. Therefore, in addition to considering the possibility of CAP due to a hypervirulent pathogen, patients who present with fever, dyspnea, leukocytosis, pulmonary infiltrates, and shock in the absence of conditions associated with hyposplenism should be evaluated for imitators of pneumonia, such as acute myocardial infarction or acute pulmonary embolism.

Conditions that predispose to severe CAP should be considered in patients presenting with CAP and shock in the absence of one of the aforementioned cardiopulmonary diseases. The following disorders and therapies have been associated with severe CAP:

• Hyposplenism, splenectomy, or congenital asplenia
• Corticosteroid therapy
• HIV/AIDS
• Chronic alcoholism
• Amyloidosis
• Chronic active hepatitis
• Fanconi syndrome
• Other causes of immunocompromise: Immunoglobulin A (IgA) deficiency, intestinal lymphangiectasia, myeloproliferative disorders, Waldenström macroglobulinemia, systemic mastocytosis
• Illnesses requiring immunosuppression: Celiac disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), vasculitis, non-Hodgkin lymphoma

• References

Patient History

Patients with community-acquired pneumonia (CAP) due to typical bacterial CAP pathogens commonly present with fever, dyspnea, and productive cough, often with pleuritic chest pain.

The clinical presentation of atypical CAP is more subacute and associated with extrapulmonary manifestations that may provide a clue to the etiology.

Zoonotic infection

Contact with the appropriate zoonotic vector or its by-product (eg, milk, urine, feces, placenta) is needed to develop a zoonotic CAP. A history of occupational exposure to livestock (eg, farmers, veterinarians) or close contact with a parturient animal should be sought in patients with suspected Q fever. Psittacosis is preceded by recent contact with birds infected with C psittaci. Occupations and avocations associated with increased risk include poultry farming, pet shops, veterinary clinics, and ownership of pet birds (classically of the psittacine, or parrot, family). Hantavirus is transmitted via exposure to wild rodents, specifically to aerosolized rodent urine or feces; thus, queries as to whether a patient presenting with severe CAP works or recreates in a setting conducive to rodent exposure (eg, farms, ranches, forests) is warranted.

• References

Physical Examination

Purulent sputum is characteristic of pneumonia caused by typical bacterial community-acquired pneumonia (CAP) pathogens and is not usually a feature of pneumonia caused by atypical pathogens, with the exception of Legionnaires disease. Blood-tinged sputum may be found in patients with pneumococcal pneumonia, Klebsiella pneumonia, or Legionella pneumonia.

Rales are heard over the involved lobe or segment. Consolidation may be accompanied by an increase in tactile fremitus, bronchial breath sounds, and egophony.

Legionella pneumonia, Q fever, and psittacosis are atypical pneumonias that may present with signs of consolidation. Consolidation is not a typical feature of pneumonia caused by M pneumoniae or C pneumoniae.^[42]

Be wary when a patient presents with severe CAP, with or without hypotension or shock. In these patients, be sure to exclude underlying immunocompromise, asplenia, or acute pulmonary or cardiac event or a particularly virulent pathogen such as influenza or S aureus that could explain the severity of the CAP.

Pleural effusion

Pleural effusion, if large enough, may be detectable on physical examination. Patients with a pleural effusion have decreased tactile fremitus, decreased breath sounds on auscultation, and dullness on chest percussion.

Empyema

On physical examination, empyema has the same findings as pleural effusion. Thoracentesis with analysis of pleural fluid for pH, cell counts, and Light criteria are helpful when differentiating simple pleural effusion from parapneumonic effusion from empyema. PCR, in addition to traditional culture methods, may be helpful to determine the bacterial pathogen, if necessary.^[52]

• References

Differential Diagnoses of Community-Acquired Pneumonia

Aside from those mentioned above, the differential diagnoses to consider in the diagnosis of community-acquired pneumonia (CAP) include the following:

• Acute bronchitis
• Acute exacerbation of chronic bronchitis
• Aspiration pneumonitis
• Myocardial infarction
• CHF and pulmonary edema
• Pulmonary fibrosis
• Sarcoidosis
• SLE pneumonitis
• Pulmonary drug hypersensitivity reactions (nitrofurantoin, daptomycin)
• Drug-induced pulmonary disease (bleomycin)
• Cryptogenic organizing pneumonia
• Pulmonary embolus or infarction
• Bronchogenic carcinomas
• Radiation pneumonitis
• Granulomatosis with polyangiitis (Wegener granulomatosis)
• Lymphoma
• Tracheobronchitis

• References

Sputum Studies and Blood Culture

Send sputum samples from patients with severe community-acquired pneumonia (CAP) for Gram stain and/or culture. Keep in mind that many patients, especially elderly persons, may not be able to produce an adequate suitable sputum sample.

Sputum Gram stain is reliable and diagnostic if performed on a well-collected specimen without many squamous epithelial cells (saliva contamination) and if a predominant organism is present. Gram stain shows few or no predominant organisms in patients with atypical CAP.

In all patients with CAP who meet criteria for hospital admission, obtain blood cultures prior to administering antibiotics because pneumonia due to some bacterial pathogens, such as S pneumoniae and H influenzae, is frequently associated with positive blood cultures. The overall yield from blood cultures is low, as viral and many bacterial pathogens such as M catarrhalis are not often associated with bacteremia.^[25]

• References

Studies in HIV-Positive Patients with Community-Acquired Pneumonia

The differential diagnoses of community-acquired pneumonia (CAP) in patients with human immunodeficiency virus (HIV) infection is broader than in HIV-negative patients. The patient’s immunologic status, as reflected by the CD4 count, the clinical course, and the chest radiographic appearance, provides clues to the most likely etiologic organism.

Patients with HIV infection and a normal or slightly decreased CD4 count with focal infiltrates have approximately the same pathogen distribution as otherwise healthy hosts (eg, S pneumoniae is most common) and thus warrant the same diagnostic strategies as the general population. Pneumocystis jiroveci pneumonia (PJP) should be suspected in patients with a CD4 count of less than 200 cells/µL (or CD4% < 14%) presenting with gradually progressive dyspnea, nonfocal infiltrates on chest radiography, nonproductive cough, and hypoxemia. A definitive diagnosis of PJP requires visualization of the PJP cysts (ie, using special stains such as Giemsa or methenamine silver); bronchoscopy with bronchoalveolar lavage (BAL) is often necessary to obtain an adequate specimen.

In the absence of an alternate etiology (such as influenza), patients with HIV infection who are admitted with CAP should be placed on airborne isolation while the possibility of active pulmonary tuberculosis is evaluated (eg, with sputum AFB smears/cultures), factoring in local incidence and potential exposure risk.

Additional uncommon CAP pathogens, such as histoplasmosis, coccidioidomycosis, and cryptococcosis, should also be considered in HIV-positive patients who present with pulmonary infiltrates, with risk stratified according to potential exposure history. Antigen testing (urine antigen for histoplasmosis; serum antigen for cryptococcosis) may be helpful in these cases.

• References

Other Laboratory Tests for Community-Acquired Pneumonia

Several nonspecific laboratory tests are often performed during the workup of community-acquired pneumonia (CAP), particularly if atypical CAP is suspected.

Serum transaminase, serum sodium, serum ferritin, serum phosphorus, and creatine phosphokinase (CPK) levels may provide evidence supporting a particular pathogen, such as Legionella. Lactic acid, white blood cell (WBC) count, blood urea nitrogen, and creatinine may be used in categorizing the severity of illness.

Cold agglutinin titers of 1:32 or greater may support a diagnosis of M pneumoniae, although this test is neither sensitive nor specific and has largely been replaced by newer diagnostic studies, such as respiratory pathogen PCR assay.

Procalcitonin and C-reactive protein levels

C-reactive protein (CRP) and procalcitonin are inflammatory biomarkers that have been extensively studied in recent years as possible adjuncts for the diagnosis and management of pneumonia.

CRP is widely available and is relatively inexpensive, although, as a nonspecific acute-phase reactant, it has limited ability to differentiate between causes of inflammation.

Procalcitonin (PCT) is a calcitonin preceptor peptide that is released in response to microbial endotoxins and pro-inflammatory cytokines triggered with bacterial infection (interleukin-1beta, tumor necrosis factor alpha, and interleukin 6), while being down-regulated by interferon gamma, a cytokine released in response to viral infections.^[11] Thus, there has been significant interest in whether procalcitonin may be able to help quickly determine a bacterial etiology of infection. PCT has shown promise in diagnosing bacterial versus nonbacterial infection, predicting CAP severity and prognosis, and guiding duration of antibiotic therapy in pneumonia. However, at this point, significant controversy remains regarding the practical utility of procalcitonin in clinical practice. Various factors contribute to the dispute, including limitations of the test itself (eg, PCT may not be systemically released in localized infections such as empyema), insufficient availability or delay in results of the PCT assay at many treating facilities, conflicting results among studies, and lack of consistent established cutpoints to guide management decisions. Further prospective studies are needed to help clarify these and other issues, such as cost-effectiveness.

Several studies to date have demonstrated PCT levels alone or in combination with CRP may help predict mortality in CAP.^[13] The time from symptom onset influences both CRP and PCT levels at the time of CAP diagnosis,^[53] which may need to be considered when determining how to apply PCT values to prognostic and/or management decisions.

A 2018 meta-analysis of patient data from 26 randomized controlled trials assessed the safety of procalcitonin-guided antibiotic decisions (relating to either initiating or continuing antibiotics) in patients with acute respiratory infections.^[54] Among the 6,708 patients whose data were included, 30-day all-cause mortality rates were significantly lower (adjusted odds ratio [aOR], 0.83 [95% CI, 0.70-0.99]) in patients who were randomized to the PCT-guided treatment arm compared to controls, as was duration of antibiotic exposure (5.7 vs 8.1 days; P < 0.001) and frequency of adverse effects due to antibiotic therapy (16% vs 22%, aOR, 0.68 [95% CI, 0.57-0.82]). However, there was not a statistically significant difference in rate of treatment failure between the PCT-guided and control groups (aOR, 0.9 [95% CI, 0.80-1.010]). This meta-analysis included a heterogenous group of respiratory tract diagnoses, including acute exacerbations of COPD and bronchitis, in addition to CAP, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Although CAP represented the most number of primary diagnoses, it comprised less than half of the cases. No significant difference in all-cause 30-day mortality rate was detected when the analysis was restricted to patients with a diagnosis of CAP (aOR, 0.82 [95% CI, 0.66-1.03]), although treatment failure (aOR, 0.78 [95% CI, 0.66-0.93] and antibiotic side effects (aOR, 0.62 [95% CI, 0.48-0.8]) were significantly less common in the PCT-guided group, yet length of ICU stay was longer (aOR, 1.45 [95% CI, 0.15-2.75]). One limitation of this meta-analysis was that adherence to the PCT algorithm varied greatly among the studies, ranging from 44%-100%. The PCT thresholds used to help guide antibiotic therapy also varied among the studies, potentially affecting applicability to clinical practice.

The 2016 IDSA/ATS guidelines on HAP/VAP recommended against the addition of either PCT or CRP to clinical criteria alone when deciding whether to initiate antibiotics, although they did provide a weak recommendation for the use of PCT levels plus clinical criteria to help guide discontinuation of antibiotics in patients with VAP.^[55] A consensus statement addressing appropriate use of PCT is expected to be an important component of the next iteration of the IDSA/ATS CAP guidelines.

Direct fluorescent antibody testing

Direct fluorescent antibody (DFA) testing of the sputum can be performed to try to assist with the diagnosis of atypical CAP pathogens, including Legionella, P jiroveci, and Chlamydophila; however, the utility of this test is hampered by suboptimal sensitivity and is relatively difficult to perform. A DFA stain showing Legionella infection is seen in the image below.

View Image

Sputum direct fluorescent antibody stain showing Legionella infection.

Serology

Serology has been replaced by more rapid PCR-based assays in many settings; serology was historically useful in identifying fastidious organisms, particularly when dealing with pathogens that have potential epidemiologic implications (ie, epidemic or biohazard situations), such as B pertussis, M pneumoniae, L pneumophila, or C burnetii. Serologic diagnosis is based on a 4-fold or greater increase in titers between acute- and convalescent-phase serum specimens so is generally not useful in the acute-care setting. A significantly elevated IgM titer (typically present in the acute phase of infection) may help support a diagnosis, and some experts have suggested that combining IgM and nucleic acid amplification testing may be the optimal method for diagnosing M pneumoniae infection.^[56]

Urinary antigen test

Pneumococcal urinary antigen testing (UAT) is a non–culture-based test for diagnosing pneumococcal infection that has a reported sensitivity of 50%-80% and specificity of more than 90%.^[57] Thus, a negative result does not rule out pneumococcal pneumonia. The UAT results remain positive after antibiotics have been started so may be particularly useful when cultures were not obtained prior to initiation of antibiotic therapy. Recent IDSA guidelines recommend use of pneumococcal urinary antigen testing in adults with severe CAP.^[7]

In 2018, Wunderink et al reported that serotype-specific urinary antigen detection assays may further improve detection of pneumococcal pneumonia in hospitalized adults with CAP.^[58] Availability of pneumococcal UAT is the main perceived barrier to its routine use.^[57]

Urinary antigen testing is considered the first-line diagnostic test for L pneumophila. The sensitivity of the test ranges from 55%-99%, with improved sensitivity paralleling disease severity.^[49] The specificity is high (95%). The urinary antigen test is applicable only for L pneumophila serogroup type I, which accounts for approximately 85% of Legionella infections in the United States and Europe. In other regions of the world, including Australia, Thailand, and New Zealand, 25% of cases have been attributed to another species, Legionella longbeachae.^[59] The urinary antigen test results remain positive for Legionella for long periods but may be negative within the first 48 hours of infection. Using a combination of Legionella UAT and PCR of respiratory secretions, which is often able to detect all species of Legionella, may increase the ability to diagnose Legionella pneumonia.^[60] The 2019 IDSA/ATS CAP guidelines recommend obtaining a urine Legionella antigen test in patients with severe CAP and when epidemiologic factors support a potential Legionella diagnosis.^[7]

Polymerase chain reaction

Polymerase chain reaction (PCR) has emerged as an important diagnostic tool for determining the etiology of CAP, particularly with regard to respiratory viruses and fastidious organisms, including Legionella, Mycoplasma, and Chlamydophila.^[2] PCR is a very sensitive and specific method for isolating these pathogens. The source of specimen may affect the diagnostic yield of PCR assays; for instance, the detection rate of many pathogens, including Legionella and M pneumoniae, is higher with sputum samples than with nasopharyngeal aspirates.^[60] However, nasopharyngeal samples remain useful, as many patients are unable to provide a quality sputum sample. The increasing commercial availability of various PCR assays (including multiplex) has allowed for increased implementation in the clinical setting. Multipathogen approaches are less expensive and more time consuming than testing each organism individually, although they may be complex to perform. Rapid molecular tests for respiratory viruses are also increasingly being developed with the goal of further shortening the time to diagnosis.^[61]

Interpreting the significance of PCR detection of an organism known to colonize the upper airway or those that may be associated with protracted shedding, such as rhinovirus, remains a challenge. Quantitative PCR methods have shown some promise in improving interpretability of such findings.^[62]

A 2016 study in the United Kingdom assessed the use of comprehensive molecular testing of a single lower respiratory tract specimen to detect a pathogen in CAP.^[63] The study compared (1) a combination of real-time multiplex PCR assays targeting 26 different pathogens, including bacteria and viruses, with (2) culture-based diagnostic testing of the same specimens. Quantification of bacterial load was performed for 8 common bacteria, including S pneumoniae, H influenzae, and M catarrhalis. A pathogen was detected in 87% of patients with CAP using the multiplex assay, whereas culture achieved a diagnosis in only 39% of cases. Viruses were detected in 30% of cases. H influenzae and S pneumoniae were the most commonly detected bacteria. Pathogen detection was not significantly decreased when a quantitative threshold for detection of ≥10⁵ CFU/mL for all bacterial loads was applied, although the mean bacterial load was lower in patients who had received prior antibiotics than in those who had not. Interestingly, of the 268 patients who received antibiotics prior to testing, 77.6% had a positive bacterial PCR finding, but only 32% were culture-positive. The authors concluded that comprehensive molecular testing on a lower respiratory tract specimen has the potential to positively affect targeted antibiotic therapy in most patients with CAP.

• References

Chest Radiography and CT Scanning

Chest radiography

Obtain chest radiographs in all patients with suspected community-acquired pneumonia (CAP) to exclude conditions that mimic CAP and to confirm the presence of an infiltrate compatible with the presentation of CAP.^{[8, 9]} (See the images below.)

View Image

Chest radiograph in a patient with HIV infection, bilateral perihilar infiltrates, and Pneumocystis jiroveci pneumonia.

View Image

Chest radiograph in a patient with HIV infection and focal infiltrates due to tuberculosis.

Chest radiography findings may be negative in patients who present very early with CAP. In these patients, repeat chest radiography within 24 hours is recommended.

Chest radiography may assist with the differentiation of viral pneumonias from nonviral pneumonias but are not specific enough alone to confirm the diagnosis. Viral pneumonias tend to display few or no infiltrates on chest radiography, but, when infiltrates are present, they are almost always bilateral, perihilar, symmetric, and interstitial. The appearance of infiltrates in viral pneumonia may be mistaken for pulmonary edema, or vice versa.

Bacterial pneumonias have a predominantly focal segmental or lobar distribution, with or without pleural effusions. Atypical bacterial pathogens have variable radiographic findings, ranging from focal segmental to bilateral interstitial disease. P jiroveci (PJP) pneumonia typically manifests as bilateral patchy interstitial infiltrates. Of note, radiographic findings alone are not reliable for differentiating specific etiologies of CAP.

Chest radiographic findings should be negative in patients with asthma or exacerbation of chronic bronchitis who do not have CAP.

The infiltrates observed with CHF appear as increased interstitial markings and show vascular redistribution to the upper lobes. Patients with preexisting heart failure usually have cardiomegaly.

Rapid cavitation is not a typical feature of CAP.

Community-acquired methicillin-resistant S aureus (CA-MRSA) CAP presents as a fulminant CAP with rapid cavitation and necrotizing pneumonia caused by CA-MRSA (SCC mec IV) with the Panton-Valentine leucocidin (PVL) gene. CA-MRSA CAP sometimes occurs after influenza but may also develop independent of influenza, even in young healthy hosts.

Serial chest radiography can be used to observe the progression of severe CAP if the patient has not improved within 5-7 days.^[7] Chest radiographic findings worsen rapidly in severe typical bacterial CAP and require a significant period to improve. It is important to note that clinical resolution occurs long before radiologic resolution.

CT scanning

Obtain a computed tomography (CT) scan of the chest if pneumonia is clinically suspected despite persistently negative chest radiographic findings to examine for viral, atypical, or mycobacterial pneumonia, particularly in immunocompromised hosts. When an underlying bronchogenic carcinoma is suspected or if any abnormalities are not consistent with the diagnosis of pneumonia, CT is helpful to examine for structural lung disease or malignancy. Immunocompromised patients may benefit from further narrowing of the differential diagnoses with chest CT scanning.

• References

Fine-Needle Aspiration and Bronchoscopy With Bronchoalveolar Lavage

Diagnostic bronchoscopy with bronchoalveolar lavage (BAL) may be useful in patients with community-acquired pneumonia (CAP) when Pneumocystis, mycobacteria, or fungal pathogens are likely. Diagnostic bronchoscopy with BAL with or without biopsy may also be useful in unresolving CAP that does not respond to appropriate therapy.

Transthoracic fine-needle aspiration (FNA) of the infiltrate can be performed and is most useful in determining the cause of nodules or noninfectious infiltrates that are not responding to antibiotic treatment.

Transtracheal aspiration (TTA) is a potentially hazardous procedure and offers no additional diagnostic information in patients with CAP.

• References

Histologic Findings

Lung sections with typical bacterial pneumonias show the progression from red hepatization to white hepatization during the resolution process. The lung is repaired or scarred after bacterial pneumonia is complete and the infectious process resolves.

• References

Hospital Care in Community-Acquired Pneumonia

Although patients with mild community-acquired pneumonia (CAP) may be treated in an ambulatory setting, patients with CAP who are moderately to severely ill should be hospitalized. Underlying comorbidities often contribute to disease severity. Patients with severe CAP require admission to an intensive care unit (ICU), prompt administration of appropriate antibiotics for CAP, and evidence-based sepsis management. Oxygen and/or ventilatory support may be required.^{[28, 64, 65, 66, 67, 68]}

• References

Pharmacologic Therapy

Most experts feel that antimicrobial coverage should be divided against typical and atypical CAP pathogens with consideration for risk of viral infection such as influenza, based on the season.^[69] Excellent practice guidelines have been promulgated by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). These resources provide evidence-based guidelines for the treatment of outpatients, inpatients, and ICU patients with CAP.^[7]

A 2017 review presented a CAP bundle that is in line with international guidelines and IDSA/ATS guidelines. The 2019 updated IDSA/ATS guidelines also support these components. The bundle includes the following:^{[5, 7]}

• Use of PSI and clinical criteria to the determine CAP severity and appropriate level of care
• Rapid empiric appropriate antibiotics started promptly
• Rapid fluid and electrolyte resuscitation, thromboembolic prophylaxis, and management of hypoxia
• Early ambulation
• Assessment of cardiovascular risk with appropriate initiation of aspirin or other prophylaxis

Adequate therapy for CAP includes coverage for S pneumoniae and atypical bacterial pathogens. Treatment options for CAP in outpatients with no comorbidities and no risk factors for drug-resistant S pneumoniae include the following:^[7]

• Amoxicillin 1 gram PO three times a day OR
• A macrolide (azithromycin 500 mg once and then 250 mg daily or clarithromycin 500 mg twice daily) OR
• Doxycycline 100 mg twice daily

During influenza season, it is also reasonable to initiate oseltamivir, zanamivir, or baloxavir therapy in outpatients who present with a flulike illness and pneumonia. Macrolides should be used only in areas where pneumococcal resistance is less than 25%.

Treatment options for CAP in patients with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia; immunosuppression; prior antibiotics within 90 days; or other risk factors for drug-resistant infection include the following:

• Beta-lactam (high-dose amoxicillin 1 g 3 times/day, amoxicillin/clavulanate 2 g/125 mg twice daily or 500 mg/125 mg three times daily or 875 mg/125 mg twice daily, cefpodoxime 200 mg twice daily, or cefuroxime 500 mg twice daily) plus a macrolide or doxycycline OR
• Respiratory fluoroquinolones (moxifloxacin 400 mg daily, levofloxacin 750 mg daily)

For hospitalized patients, therapy consists of the following:

• Beta-lactams (ampicillin/sulbactam 1.5-3 g every 6 hours, ceftriaxone 1-2 g daily, cefotaxime 1-2 g every 8 hours, or ceftaroline 600 mg every 12 hours) plus a macrolide OR
• Respiratory fluoroquinolone OR
• If macrolides and fluoroquinolones are contraindicated: beta-lactam as above plus doxycycline

Recent studies have failed to show that the use of a beta-lactam alone is noninferior to a beta-lactam/macrolide combination for time to clinical stability and other safety parameters in hospitalized patients.^[70]

Therapy in ICU patients includes the following:

• Beta-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) plus either a macrolide or respiratory fluoroquinolone
• In patients with penicillin allergy, a respiratory fluoroquinolone and aztreonam

Risk factors for Pseudomonas pneumonia include structural lung disease, COPD, and bronchiectasis.^[4] If Pseudomonas is suspected, therapy consists of an anti-pneumococcal and anti-pseudomonal beta-lactam (piperacillin/tazobactam 4.5 g every 6 hours, cefepime 2 g every 8 hours, ceftazidime 2 g every 8 hours, aztreonam 2 g every 8 hours, meropenem 1 g every 8 hours, or imipenem 500 mg every 6 hours.

In patients with severe penicillin allergy, aztreonam may be used instead of the beta-lactam in the regimen listed above. It is worth noting that many reported penicillin allergies are not true allergies. Owing to the limited spectrum of aztreonam and the relatively low likelihood of penicillin allergy cross-reacting with cephalosporins (2%), cefepime is a reasonable choice after considering the balance of benefit and risk.^[17]

Doripenem is no longer recommended for ventilator-acquired pneumonia (VAP) and is not FDA-approved for treating any kind of pneumonia.^[18]

If MRSA is suspected, vancomycin 15 mg/kg every 12 hours adjusted based on levels or linezolid 600 mg every 12 hours should be added. Risk factors for MRSA include hemoptysis, recent influenza, neutropenia, hemodialysis, and congestive heart failure.^[4] During influenza season, it is also reasonable to start oseltamivir, zanamivir, peramivir, or baloxavir therapy to treat influenza in patients with MRSA CAP, as well as in patients who present with a flulike illness and pneumonia, as influenza may have preceded the MRSA infection.

Mild to moderately ill patients with CAP may be treated entirely via the oral route, on either an inpatient or outpatient basis. Patients receiving oral antibiotics may be admitted for hospital services (eg, pulmonary toilet and additional diagnostic tests) that are not obtainable on an outpatient basis. Patients who are severely ill or unable to tolerate or absorb oral medications require a longer duration of intravenous therapy before switching to an oral antibiotic.^[24]

If the patient is switched to an oral regimen and is doing well, earlier discharge from the hospital is possible. The oral therapy regimen can be completed at home. Optimal intravenous-to-oral switch therapy consists of a single agent that has an appropriate spectrum, has excellent bioavailability, is well tolerated, has a low resistance potential, and is relatively inexpensive.

Newer agents approved or under investigation for treatment of CAP include omadacycline, lefamulin, solithromycin, ceftaroline, nemonoxacin, and delafloxacin. Omadacycline is a tetracycline designed to overcome tetracycline resistance, and it was shown to be noninferior to moxifloxacin.^{[71, 72]} Lefamulin, a pleuromutilin antibiotic, was found to be noninferior to moxifloxacin in a 2019 phase 3 trial.^[73] Lefamulin is indicated for the treatment of bacterial CAP due to S pneumoniae, S aureus (methicillin-susceptible isolates), H influenzae, Legionella pneumophila, M pneumoniae, or C pneumoniae in adults. It is administered twice daily as either an intravenous infusion or an oral tablet. Solithromycin, a new macrolide, was compared to moxifloxacin as an IV-to-PO option and was found to be noninferior.^[74] Ceftaroline has been shown noninferior and possibly superior to ceftriaxone for CAP in randomized, controlled, double-blind, international trials based in the United States and Asia.^{[75, 76]} Nemonoxacin has been reported to yield clinical cure rates similar to those of levofloxacin in 3 trials, primarily in Asia and Russia.^[77] Delafloxacin, a novel fluoroquinolone, has the advantage of activity against both MRSA and Pseudomonas and gained approval in October 2019 for the treatment of bacterial CAP in adults. Approval was based on a phase 3 randomized, double-blind study (n = 859) that compared delafloxacin to moxifloxacin. Results showed that IV-to-oral delafloxacin was noninferior at 96 hours compared with moxifloxacin.^{[78, 79]}

Baloxavir is a promising agent that was recently globally approved for influenza. It is a selective inhibitor of influenza cap-dependent endonuclease and is active against both influenza A and B. It has activity against resistant strains and was superior to placebo in alleviating symptoms and superior to oseltamivir for rapid reduction of viral load.^[80]

Mild to moderately ill patients with CAP may be treated entirely via the oral route, on either an inpatient or outpatient basis. The duration of therapy for uncomplicated CAP is usually 5 days.^{[25, 19]} The duration of therapy for CAP due to suspected or proven Pseudomonas or MRSA should be 7 days. Patients should be afebrile for 48-72 hours and have no signs of instability before antibiotic therapy is stopped. The duration of therapy may need to be increased if the initial empiric therapy has no activity against the specific pathogen or if the pneumonia is complicated by extrapulmonary infection.^[25] The use of systemic corticosteroids in patients with CAP is not supported routinely but may be useful for managing certain comorbidities or as part of the sepsis bundle. Studies have shown that corticosteroids may reduce the length of time until clinical stability, decrease hospital length of stay, lessen the need for mechanical ventilation, and lower the incidence of adult respiratory distress syndrome.^{[81, 82]} These potential benefits should be weighed against the risk of worsening influenza pneumonia or causing hyperglycemia.^[5] Furthermore, there is insufficient data or agreement on the dose or duration of the steroid therapy.

Comorbid conditions

Comorbid conditions affect a patient’s risk of contracting CAP caused by MRSA, Pseudomonas, or other antibiotic-resistant pathogens. Risks for antibiotic-resistant pathogens include hospital admission within the preceding 90 days, antibiotics in the preceding 90 days, septic shock at the time of CAP, immunosuppression, enteral tube feedings, nonambulatory status, or gastric acid suppression. MRSA risk factors include all of the prior plus hemodialysis, CHF, and a history of MRSA colonization.^{[55, 5]} Comorbidities represent an important prognostic factor and contribute to the severity index.^[47]

Severity

The Pneumonia Severity Index (PSI) is preferred over the CURB-65 (confusion, uremia, respiratory rate, low blood pressure, age >65 years) for determining outpatient verses inpatient treatment. Patients with PSI class IV-V may need hospitalization or more intensive in-home services. Severe pneumonia is defined as having 1 major criteria (ie, septic shock requiring vasopressors or respiratory failure requiring mechanical ventilation) or 3 minor criteria, as follows:

• Respiratory rate of 30 or more breaths per minute
• PaO₂/FIO₂ ratio of 250 or less
• Multilobar infiltrates
• Confusion
• Uremia
• Leukopenia (WBC < 4000 cells/µl)
• Thrombocytopenia (platelet count < 100,000/µl)
• Hypothermia
• Hypotension

These are the primary criteria to use to determine if a patient requires ICU admission. CURB-65 was designed to predict mortality risk; CRB-65 is similar but is used when certain laboratory tests are unavailable. Some scoring systems (eg, CURXO and SMART-COP) focus on the severity of CAP and likelihood of requiring ventilatory or circulatory support, whereas others (eg, PSI score) help determine whether CAP requires hospitalization.

Appropriate spectrum

In otherwise healthy hosts with CAP, therapy does not need to cover S aureus, Klebsiella species, or P aeruginosa. Coverage should include typical (S pneumoniae, H influenzae, M catarrhalis) and atypical (Legionella and Mycoplasma species, C pneumoniae) pathogens. S aureus coverage should be included in patients with influenza who have focal infiltrates or patients who have risk factors for MRSA pneumonia such as prior hospital admission of 2 or more days in the preceding 90 days, antibiotics in the preceding 90 days, residence in a long-term care facility, septic shock at the time of CAP, immunosuppression, enteral tube feedings, nonambulatory status, gastric acid suppression, chronic hemodialysis, congestive heart failure, and history of MRSA colonization.^{[5, 55]}

Most antibiotics used to treat community-acquired aspiration pneumonia (eg, beta-lactam/beta-lactamase inhibitor) are highly effective against oral anaerobes. For aerobic lung abscesses, clindamycin or moxifloxacin is preferable.^{[83, 84, 85, 86]}

Monotherapy

Preferred monotherapy for mild or outpatient CAP includes a macrolide, amoxicillin, or doxycycline. For patients with an increased risk of resistance or with numerous comorbidities, monotherapy options include respiratory quinolone. Prior to the use of a fluoroquinolone, an assessment of contraindications and risk of adverse effects should be performed.

Penicillin resistance

Most penicillin-resistant S pneumoniae infections may be treated with beta-lactams. Alternately, doxycycline or respiratory quinolones may be used.

High-level penicillin-resistant S pneumoniae (MIC 6 µg/mL) strains are a rare cause of CAP; fortunately, they currently remain susceptible to ceftriaxone.

Proton-pump inhibitors

There is conflicting evidence as to the safety of using PPIs and H2 blockers.^{[87, 88, 89, 90]} Some studies have concluded that PPI use increases the risk of pneumonia or even the risk of multidrug-resistant pathogens causing pneumonia. Other, more recent, studies find such links may have been resulted from confounding factors.^{[91, 89]}

PPIs were associated with an increased risk of C difficile colitis compared with H2 blockers.^[92]

• References

Outpatient Care in Community-Acquired Pneumonia

Patients with mild community-acquired pneumonia (CAP) who are being treated on an outpatient basis should be monitored to ensure compliance with their medications and to ensure clinical improvement. After 1 week, a repeat visit is advisable. If the patient is improving and parapneumonic complications are not evident, posttherapy chest radiography is unnecessary.^{[93, 94, 95]}

The diet in patients with CAP is as tolerated. Guide activity with common sense.

• References

Vaccination

Pneumococcal vaccines have been shown to have some efficacy in preventing vaccine-strain pneumococcal pneumonia, bacteremia, and invasive disease. They have not been shown to prevent community-acquired pneumonia (CAP) of all kinds.^{[96, 97]} Annual influenza vaccination has been shown to decrease pneumonia diagnoses, hospitalizations, and cardiac events in certain populations.^{[98, 99, 100, 101]}

Annual influenza vaccination is recommended in all persons older than 6 months. There are several options for vaccination, including standard-dose trivalent inactivated vaccine, high-dose inactivated trivalent vaccine, three different formulations of quadrivalent inactivated vaccine (egg-based, cell culture–based, and recombinant-derived), and a live attenuated influenza vaccine. Per current CDC recommendations, people with a history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine.^[102] Individuals with a history of severe egg allergy should receive the vaccine under the supervision of a physician experienced in the management of allergic conditions. People with a personal history of severe allergy to the flu vaccine should not receive it, and persons with history of Guillain-Barré syndrome should consult with their physician prior to being vaccinated.^[103]

Two pneumococcal vaccines are approved in the United States; 13-valent polysaccharide conjugate vaccine (PCV13; Prevnar 13) is approved for children aged 6 weeks to 17 years and adults aged 50 years or older. The 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23) is approved for adults aged 65 years or older and persons aged 2 years or older who are at an increased risk for pneumococcal disease.

The Advisory Committee on Immunization Practices (ACIP) recommends routine use of PCV13 in addition to PPSV23 for adults older than 65 years. It is recommended that an initial dose of PCV13 be given, followed by PPSV23 at least one year later. If PPSV23 has already been given, it should be followed by PCV13 a year later. A second dose of PPSV23 is not needed in immunocompetent hosts. If PPSV23 is inadvertently given prior to 1 year after PCV13, it does not need to be repeated.

In adults aged 19 years and older with immunocompromising conditions (eg, HIV, cancer, renal disease), functional or anatomic asplenia, cerebrospinal fluid leaks, or cochlear implants, it is recommended that they receive PCV13, followed by PPSV23 at least 8 weeks later. In patients who have previously received PPSV23 vaccine, administer 1 dose of PCV13 at least 1 year after the last PPSV23 dose. A second dose of PPSV23 is recommended 5 years after the first dose in persons in this category aged 19-64 years. If the first dose of PPSV23 was administered prior to age 65 years, an additional dose should be administered at age 65 years or at least 5 years after the prior dose. Subsequent doses of PPSV23 should not be given sooner than 8 weeks after a dose of PCV13 and 5 years after the most recent dose of PPSV23.^[104]

Nonleukopenic compromised hosts, such as those with rheumatoid arthritis, SLE, or alcoholism, may not develop an antibody response to the pneumococcal vaccine and may therefore remain susceptible to pneumococcal pneumonia. The same is true concerning the use of the Haemophilus vaccine.

• References

Infectious Diseases Society of America/American Thoracic Society CAP Guidelines

The Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS) issued updated clinical practice guidelines for community-acquired pneumonia (CAP) in October 2019.^[7]

Diagnosis

Gram stain and sputum culture

Routine sputum culture and Gram stain are not recommended in adult outpatients with community-acquired pneumonia (CAP).

In hospitalized patients, pretreatment Gram stain and culture of respiratory secretions are recommended in adults with CAP that is considered severe (particularly in intubated patients) or who meet one of the following conditions:

• Is currently receiving empiric treatment for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa
• Previously had MRSA or P aeruginosa infection, especially of the respiratory tract
• Was hospitalized within the preceding 90 days and received parenteral antibiotics for any reason

Blood culture

Blood cultures are not recommended in adult outpatients with CAP.

Routine blood cultures are not recommended in hospitalized adults with CAP.

Pretreatment blood cultures are recommended in hospitalized adults with CAP that is classified as severe or who meet one of the following conditions:

• Is currently receiving empiric treatment for MRSA or P aeruginosa
• Previously had MRSA or P aeruginosa infection, especially of the respiratory tract
• Was hospitalized within the preceding 90 days and received parenteral antibiotics for any reason

Legionella and pneumococcal urinary antigen testing

Routine urine testing for pneumococcal antigen is not recommended in adults with CAP unless the CAP is severe.

Routine urine testing for Legionella antigen is not recommended in adults with CAP unless the CAP is severe or as indicated based on predisposing epidemiological factors (eg, Legionella outbreak or recent travel).

Legionella testing should consist of urinary antigen assessment and collection of lower respiratory tract secretions for culture on selective media or nucleic acid amplification.

Influenza testing

If influenza is circulating in the community, influenza testing in adults with CAP is recommended with a rapid influenza molecular assay, which is preferred over a rapid influenza diagnostic test.

Procalcitonin testing

Empiric antibiotic therapy is recommended in adults with clinically suspected and radiographically confirmed CAP, regardless of the patient’s initial serum procalcitonin level.

Treatment

Decision for hospitalization

The decision for hospitalization in adults with CAP should be based on clinical judgement plus a validated clinical prediction rule for prognosis. The Pneumonia Severity Index (PSI) is preferred over the CURB-65.

ICU admission

Direct ICU admission is recommended for patients with CAP who have hypotension requiring vasopressors or respiratory failure requiring mechanical ventilation.

In patients who do not require vasopressors or a mechanical ventilator, the IDSA/ATS 2007 minor severity criteria, along with clinical judgment, are suggested for deciding whether to escalate treatment intensity.

Outpatient antibiotic regimens

The following antibiotics are recommended in adult patients with CAP who are otherwise healthy:

• Amoxicillin 1 g three times daily OR
• Doxycycline 100 mg twice daily OR
• In areas with pneumococcal resistance to macrolides < 25%: a macrolide (azithromycin 500 mg on day one and then 250 mg daily or clarithromycin 500 mg twice daily or clarithromycin extended-release 1,000 mg daily)

In outpatient adults with CAP who have comorbidities, the following antibiotic regimens are recommended:

• • Amoxicillin/clavulanate 500 mg/125 mg 3 times daily OR amoxicillin/clavulanate 875 mg/125 mg twice daily OR 2,000 mg/125 mg twice daily OR a cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily) PLUS
  • A macrolide (azithromycin 500 mg on day one then 250 mg daily, clarithromycin [500 mg twice daily or extended release 1,000 mg once daily]) or doxycycline 100 mg twice daily OR

   

  

   
• Monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily)

Inpatient antibiotic regimens

The following empiric treatment regimens are recommended in inpatient adults with nonsevere CAP who do not have risk factors for MRSA or P aeruginosa:

• Combination therapy with a beta-lactam (ampicillin plus sulbactam 1.5-3 g every 6 hours, cefotaxime 1-2 g every 8 hours, ceftriaxone 1-2 g daily, or ceftaroline 600 mg every 12 hours) and a macrolide (azithromycin 500 mg daily or clarithromycin 500 mg twice daily) OR
• Monotherapy with a respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily)

The following regimens are recommended among inpatient adults with severe CAP without risk factors for MRSA or P aeruginosa:

• A beta-lactam plus a macrolide OR
• A beta-lactam plus a respiratory fluoroquinolone

Anaerobic coverage for suspected aspiration pneumonia

Routine addition of anaerobic coverage for suspected aspiration pneumonia is not recommended except when lung abscess or empyema is suspected.

Extended-spectrum antibiotic therapy for MRSA or P aeruginosa

For guiding selection of extended-spectrum antibiotic coverage in adults with CAP, the prior categorization of healthcare-associated pneumonia (HCAP) should be abandoned.

Empiric coverage for MRSA or P aeruginosa is recommended in adults with CAP only in the presence of locally validated risk factors. Empiric treatment options for MRSA include vancomycin (15 mg/kg every 12 hours) or linezolid (600 mg every 12 hours). Empiric treatment options for P aeruginosa include piperacillin-tazobactam (4.5 g every 6 hours), cefepime (2 g every 8 hours), ceftazidime (2 g every 8 hours), aztreonam (2 g every 8 hours), meropenem (1 g every 8 hours), or imipenem (500 mg every 6 hours).

If empiric coverage for MRSA or P aeruginosa is being administered to adults with CAP based on published risk factors without local etiological data, empiric coverage should be continued while culture data are obtained.

Corticosteroid therapy

Routine corticosteroid treatment is not recommended in adults with CAP (regardless of severity) or severe influenza pneumonia.

The ATS/IDSA CAP guidelines endorse the Surviving Sepsis Campaign recommendations on using corticosteroids in patients with CAP who have refractory septic shock.

Anti-influenza therapy

Anti-influenza treatment (eg, oseltamivir) should be prescribed to all adults with CAP, regardless of hospitalization status, who test positive for influenza.

Antibacterial therapy in patients with influenza

Standard antibacterial treatment should be initially prescribed to adults with clinical and radiographic evidence of CAP who test positive for influenza.

Treatment duration

The duration of antibiotic therapy should be guided by a validated measure of clinical stability, continued until stability is achieved for at least 5 days.

Follow-up chest imaging

Routine follow-up chest imaging is not recommended in adults with CAP whose symptoms have resolved within 5-7 days.

• References

Patient Instructions

Remind patients with community-acquired pneumonia (CAP) to comply with prescribed antimicrobials even after they experience clinical improvement. Avoid dampening the cough reflex, and, except in patients with heart failure, encourage hydration to help facilitate clearance of secretions.

• References

Acknowledgments

The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD), or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.

• References

Author

Stephanie L Baer, MD, Associate Professor of Medicine, Division of Infectious Diseases, Department of Medicine, Medical College of Georgia at Augusta University; Hospital Epidemiologist, VA Augusta Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Rhonda E Colombo, MD, MHS, FACP, FIDSA, Clinical Research Physician, Henry M Jackson Foundation (HJF) for the Advancement of Military Medicine, In Support of Infectious Disease Clinical Research Program (IDCRP), Associate Professor, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Disclosure: Received royalty from Baxter International for other.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Disclosure: Nothing to disclose.

Additional Contributors

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Disclosure: Nothing to disclose.

Fred A Lopez, MD, Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine

Disclosure: Nothing to disclose.

Jose A Vazquez, MD, FACP, FIDSA, Chief, Division of Infectious Diseases, Professor, Department of Medicine, Medical College of Georgia at Augusta University

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cidara; Amplyx; F2G<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan; Astellas.

References

1. Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015 Jul 30. 373 (5):415-27. [View Abstract]
2. Musher DM, Thorner AR. Community-acquired pneumonia. N Engl J Med. 2014 Oct 23. 371 (17):1619-28. [View Abstract]
3. Cunha BA. Swine Influenza (H1N1) Pneumonia: Clinical Considerations. Infect Dis Clin N Am. 2010. 24:203-228.
4. [Guideline] Wunderink RG. Guidelines to Manage Community-Acquired Pneumonia. Clin Chest Med. 2018 Dec. 39 (4):723-731. [View Abstract]
5. Wunderink RG, Waterer G. Advances in the causes and management of community acquired pneumonia in adults. BMJ. 2017 Jul 10. 358:j2471. [View Abstract]
6. Huijskens EG, Koopmans M, Palmen FM, van Erkel AJ, Mulder PG, Rossen JW. The value of signs and symptoms in differentiating between bacterial, viral and mixed aetiology in patients with community-acquired pneumonia. J Med Microbiol. 2014 Mar. 63 (Pt 3):441-52. [View Abstract]
7. [Guideline] Metlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, 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 Oct 1. 200 (7):e45-e67. [View Abstract]
8. Boersma WG, Daniels JM, Löwenberg A, Boeve WJ, van de Jagt EJ. Reliability of radiographic findings and the relation to etiologic agents in community-acquired pneumonia. Respir Med. 2006 May. 100(5):926-32. [View Abstract]
9. Bruns AH, Oosterheert JJ, Prokop M, Lammers JW, Hak E, Hoepelman AI. Patterns of resolution of chest radiograph abnormalities in adults hospitalized with severe community-acquired pneumonia. Clin Infect Dis. 2007 Oct 15. 45(8):983-91. [View Abstract]
10. Liu JL, Xu F, Hui Zhou, Wu XJ, Shi LX, Lu RQ, et al. Expanded CURB-65: a new score system predicts severity of community-acquired pneumonia with superior efficiency. Sci Rep. 2016 Mar 18. 6:22911. [View Abstract]
11. Sungurlu S, Balk RA. The Role of Biomarkers in the Diagnosis and Management of Pneumonia. Clin Chest Med. 2018 Dec. 39 (4):691-701. [View Abstract]
12. Kim MW, Lim JY, Oh SH. Mortality prediction using serum biomarkers and various clinical risk scales in community-acquired pneumonia. Scand J Clin Lab Invest. 2017 Nov. 77 (7):486-492. [View Abstract]
13. Savvateeva EN, Rubina AY, Gryadunov DA. Biomarkers of Community-Acquired Pneumonia: A Key to Disease Diagnosis and Management. Biomed Res Int. 2019. 2019:1701276. [View Abstract]
14. Guo S, Mao X, Liang M. The moderate predictive value of serial serum CRP and PCT levels for the prognosis of hospitalized community-acquired pneumonia. Respir Res. 2018 Oct 1. 19 (1):193. [View Abstract]
15. Kim B, Kim J, Jo YH, Lee JH, Hwang JE, Park MJ, et al. Prognostic value of pneumococcal urinary antigen test in community-acquired pneumonia. PLoS One. 2018. 13 (7):e0200620. [View Abstract]
16. Lin FM, Feng JY, Fang WF, Wu CL, Yu CJ, Lin MC, et al. Impact of prior pulmonary tuberculosis in treatment outcomes of HCAP and CAP patients in intensive care units. J Microbiol Immunol Infect. 2019 Apr. 52 (2):320-328. [View Abstract]
17. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019 Jan 15. 321 (2):188-199. [View Abstract]
18. FDA. FDA Drug Safety Communication: FDA approves label changes for antibacterial Doribax (doripenem) describing increased risk of death for ventilator patients with pneumonia. FDA. Available at https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-approves-label-changes-antibacterial-doribax-doripenem-describing. February 26, 2018; Accessed: July 2019.
19. Wunderink RG, Waterer GW. Clinical practice. Community-acquired pneumonia. N Engl J Med. 2014 Feb 6. 370 (6):543-51. [View Abstract]
20. Blasi F, Tarsia P. Value of short-course antimicrobial therapy in community-acquired pneumonia. Int J Antimicrob Agents. 2005 Dec. 26 Suppl 3:S148-55. [View Abstract]
21. Dunbar LM, Khashab MM, Kahn JB, Zadeikis N, Xiang JX, Tennenberg AM. Efficacy of 750-mg, 5-day levofloxacin in the treatment of community-acquired pneumonia caused by atypical pathogens. Curr Med Res Opin. 2004 Apr. 20(4):555-63. [View Abstract]
22. Harrington Z, Barnes DJ. One drug or two? Step-down therapy after i.v. antibiotics for community-acquired pneumonia. Intern Med J. 2007 Nov. 37(11):767-71. [View Abstract]
23. Scalera NM, File TM Jr. How long should we treat community-acquired pneumonia?. Curr Opin Infect Dis. 2007 Apr. 20(2):177-81. [View Abstract]
24. Aliberti S, Blasi F, Zanaboni AM, Peyrani P, Tarsia P, Gaito S, et al. Duration of antibiotic therapy in hospitalised patients with community-acquired pneumonia. Eur Respir J. 2010 Jul. 36(1):128-34. [View Abstract]
25. [Guideline] Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, 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 Mar 1. 44 Suppl 2:S27-72. [View Abstract]
26. Alvarez-Lerma F, Torres A. Severe community-acquired pneumonia. Curr Opin Crit Care. 2004 Oct. 10(5):369-74. [View Abstract]
27. Brown SM, Jones BE, Jephson AR, Dean NC. Validation of the Infectious Disease Society of America/American Thoracic Society 2007 guidelines for severe community-acquired pneumonia. Crit Care Med. 2009 Dec. 37(12):3010-6. [View Abstract]
28. Carron M, Freo U, Zorzi M, Ori C. Predictors of failure of noninvasive ventilation in patients with severe community-acquired pneumonia. J Crit Care. 2010 Sep. 25(3):540.e9-14. [View Abstract]
29. Cunha BA. Severe Community-acquired Pneumoniae in the Critical Care Unit. Cunha BA (ed). Infectious Disease in Critical Care Medicine. 3rd Ed. New York, New York: Informa Healthcare; 2010. pp. 164-177.
30. Cilli A, Cakin O, Aksoy E, Kargin F, Adiguzel N, Karakurt Z, et al. Acute cardiac events in severe community-acquired pneumonia: A multicenter study. Clin Respir J. 2018 Jul. 12 (7):2212-2219. [View Abstract]
31. Reyes LF, Restrepo MI, Hinojosa CA, Soni NJ, Anzueto A, Babu BL, et al. Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling. Am J Respir Crit Care Med. 2017 Sep 1. 196 (5):609-620. [View Abstract]
32. Perry TW, Pugh MJ, Waterer GW, Nakashima B, Orihuela CJ, Copeland LA, et al. Incidence of cardiovascular events after hospital admission for pneumonia. Am J Med. 2011 Mar. 124 (3):244-51. [View Abstract]
33. Postma DF, Spitoni C, van Werkhoven CH, van Elden LJR, Oosterheert JJ, Bonten MJM. Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial. BMC Infect Dis. 2019 Jan 7. 19 (1):17. [View Abstract]
34. Nakanishi M, Yoshida Y, Takeda N, Hirana H, Horita T, Shimizu K, et al. Significance of the progression of respiratory symptoms for predicting community-acquired pneumonia in general practice. Respirology. 2010 Aug. 15(6):969-74. [View Abstract]
35. Holter JC, Müller F, Bjørang O, Samdal HH, Marthinsen JB, Jenum PA, et al. Etiology of community-acquired pneumonia and diagnostic yields of microbiological methods: a 3-year prospective study in Norway. BMC Infect Dis. 2015 Feb 15. 15:64. [View Abstract]
36. Musher DM, Abers MS, Bartlett JG. Evolving Understanding of the Causes of Pneumonia in Adults, With Special Attention to the Role of Pneumococcus. Clin Infect Dis. 2017 Oct 30. 65 (10):1736-1744. [View Abstract]
37. Howard LS, Sillis M, Pasteur MC, Kamath AV, Harrison BD. Microbiological profile of community-acquired pneumonia in adults over the last 20 years. J Infect. 2005 Feb. 50(2):107-13. [View Abstract]
38. Self WH, Wunderink RG, Williams DJ, Zhu Y, Anderson EJ, Balk RA, et al. Staphylococcus aureus Community-acquired Pneumonia: Prevalence, Clinical Characteristics, and Outcomes. Clin Infect Dis. 2016 Aug 1. 63 (3):300-9. [View Abstract]
39. Cilloniz C, Ewig S, Ferrer M, et al. Community acquired polymicrobial pneumonia in the intensive care unit: aetiology and prognosis. Crit Care. 2011 Sep 14. 15(5):R209. [View Abstract]
40. Burk M, El-Kersh K, Saad M, Wiemken T, Ramirez J, Cavallazzi R. Viral infection in community-acquired pneumonia: a systematic review and meta-analysis. Eur Respir Rev. 2016 Jun. 25 (140):178-88. [View Abstract]
41. Lim YK, Kweon OJ, Kim HR, Kim TH, Lee MK. Impact of bacterial and viral coinfection in community-acquired pneumonia in adults. Diagn Microbiol Infect Dis. 2019 May. 94 (1):50-54. [View Abstract]
42. Burillo A, Bouza E. Chlamydophila pneumoniae. Infect Dis Clin North Am. 2010 Mar. 24(1):61-71. [View Abstract]
43. Heron M. Deaths: Leading Causes for 2015. National Vital Statistics Reports. Available at https://www.cdc.gov/nchs/data/nvsr/nvsr66/nvsr66_05.pdf. November 27, 2017; Accessed: September 2019.
44. Brown JD, Harnett J, Chambers R, Sato R. The relative burden of community-acquired pneumonia hospitalizations in older adults: a retrospective observational study in the United States. BMC Geriatr. 2018 Apr 16. 18 (1):92. [View Abstract]
45. Teramoto S, Yamamoto H, Yamaguchi Y, Hanaoka Y, Ishii M, Hibi S, et al. Lower respiratory tract infection outcomes are predicted better by an age >80 years than by CURB-65. Eur Respir J. 2008 Feb. 31 (2):477-8; author reply 478. [View Abstract]
46. Marrie TJ, Poulin-Costello M, Beecroft MD, Herman-Gnjidic Z. Etiology of community-acquired pneumonia treated in an ambulatory setting. Respir Med. 2005 Jan. 99(1):60-5. [View Abstract]
47. Falguera M, Pifarre R, Martin A, Sheikh A, Moreno A. Etiology and outcome of community-acquired pneumonia in patients with diabetes mellitus. Chest. 2005 Nov. 128(5):3233-9. [View Abstract]
48. Baum S. Mycoplasma pneumoniae and atypical pneumonia. Mandell, Bennett, & Dolin, eds. Principles and Practice of Infectious Diseases. 7th ed. Churchill Livingstone; 2010. Chapter 185.
49. Cunha BA, Burillo A, Bouza E. Legionnaires' disease. Lancet. 2016 Jan 23. 387 (10016):376-85. [View Abstract]
50. Anderson A, Bijlmer H, Fournier PE, Graves S, Hartzell J, Kersh GJ, et al. Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group. MMWR Recomm Rep. 2013 Mar 29. 62 (RR-03):1-30. [View Abstract]
51. Marrie TJ, Raoult D. Coxiella burnetti (Q fever). Mandell G, BennettJ, Dolin R, eds. PPID. 7th ed. Churchill Livingstone; 2009. Chapter 189.
52. Johansson N, Vondracek M, Backman-Johansson C, Sköld MC, Andersson-Ydsten K, Hedlund J. The bacteriology in adult patients with pneumonia and parapneumonic effusions: increased yield with DNA sequencing method. Eur J Clin Microbiol Infect Dis. 2019 Feb. 38 (2):297-304. [View Abstract]
53. Méndez R, Menéndez R, Cillóniz C, Amara-Elori I, Amaro R, González P, et al. Initial Inflammatory Profile in Community-acquired Pneumonia Depends on Time since Onset of Symptoms. Am J Respir Crit Care Med. 2018 Aug 1. 198 (3):370-378. [View Abstract]
54. Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. Lancet Infect Dis. 2018 Jan. 18 (1):95-107. [View Abstract]
55. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, 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 Sep 1. 63 (5):e61-e111. [View Abstract]
56. Loens K, Ieven M. Mycoplasma pneumoniae: Current Knowledge on Nucleic Acid Amplification Techniques and Serological Diagnostics. Front Microbiol. 2016. 7:448. [View Abstract]
57. Harris AM, Beekmann SE, Polgreen PM, Moore MR. Rapid urine antigen testing for Streptococcus pneumoniae in adults with community-acquired pneumonia: clinical use and barriers. Diagn Microbiol Infect Dis. 2014 Aug. 79 (4):454-7. [View Abstract]
58. Wunderink RG, Self WH, Anderson EJ, Balk R, Fakhran S, Courtney DM, et al. Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays. Clin Infect Dis. 2018 May 2. 66 (10):1504-1510. [View Abstract]
59. Cillóniz C, Torres A, Niederman M, van der Eerden M, Chalmers J, Welte T, et al. Community-acquired pneumonia related to intracellular pathogens. Intensive Care Med. 2016 Sep. 42 (9):1374-86. [View Abstract]
60. Waterer GW. Diagnosing Viral and Atypical Pathogens in the Setting of Community-Acquired Pneumonia. Clin Chest Med. 2017 Mar. 38 (1):21-28. [View Abstract]
61. Kuypers J. Impact of Rapid Molecular Detection of Respiratory Viruses on Clinical Outcomes and Patient Management. J Clin Microbiol. 2019 Apr. 57 (4):[View Abstract]
62. Huijskens EG, Rossen JW, Kluytmans JA, van der Zanden AG, Koopmans M. Evaluation of yield of currently available diagnostics by sample type to optimize detection of respiratory pathogens in patients with a community-acquired pneumonia. Influenza Other Respir Viruses. 2014 Mar. 8 (2):243-9. [View Abstract]
63. Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF, et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. 2016 Apr 1. 62 (7):817-23. [View Abstract]
64. Davydov L, Ebert SC, Restino M, Gardner M, Bedenkop G, Uchida KM. Prospective evaluation of the treatment and outcome of community-acquired pneumonia according to the Pneumonia Severity Index in VHA hospitals. Diagn Microbiol Infect Dis. 2006 Apr. 54(4):267-75. [View Abstract]
65. Fishbane S, Niederman MS, Daly C, Magin A, Kawabata M, de Corla-Souza A. The impact of standardized order sets and intensive clinical case management on outcomes in community-acquired pneumonia. Arch Intern Med. 2007 Aug 13-27. 167(15):1664-9. [View Abstract]
66. Marrie TJ, Huang JQ. Low-risk patients admitted with community-acquired pneumonia. Am J Med. 2005 Dec. 118(12):1357-63. [View Abstract]
67. Marrie TJ, Shariatzadeh MR. Community-acquired pneumonia requiring admission to an intensive care unit: a descriptive study. Medicine (Baltimore). 2007 Mar. 86(2):103-11. [View Abstract]
68. Yoshimoto A, Nakamura H, Fujimura M, Nakao S. Severe community-acquired pneumonia in an intensive care unit: risk factors for mortality. Intern Med. 2005 Jul. 44(7):710-6. [View Abstract]
69. Genné D, Sommer R, Kaiser L, Saaïdia A, Pasche A, Unger PF. Analysis of factors that contribute to treatment failure in patients with community-acquired pneumonia. Eur J Clin Microbiol Infect Dis. 2006 Mar. 25(3):159-66. [View Abstract]
70. Garin N, Genné D, Carballo S, Chuard C, Eich G, Hugli O, 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 Dec. 174 (12):1894-901. [View Abstract]
71. Nuzyra (omadacycline) [package insert]. Boston, MA: Paratek Pharmaceuticals, Inc. 2018 October. Available at
72. Stets R, Popescu M, Gonong JR, Mitha I, Nseir W, Madej A, et al. Omadacycline for Community-Acquired Bacterial Pneumonia. N Engl J Med. 2019 Feb 7. 380 (6):517-527. [View Abstract]
73. File TM Jr, Goldberg L, Das A, Sweeney C, Saviski J, Gelone SP, et al. Efficacy and Safety of IV-to-Oral Lefamulin, a Pleuromutilin Antibiotic, for Treatment of Community-Acquired Bacterial Pneumonia: The Phase 3 LEAP 1 Trial. Clin Infect Dis. 2019 Feb 4. [View Abstract]
74. File TM Jr, Rewerska B, Vucinic-Mihailovic V, Gonong JRV, Das AF, Keedy K, et al. SOLITAIRE-IV: A Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-Acquired Bacterial Pneumonia. Clin Infect Dis. 2016 Oct 15. 63 (8):1007-1016. [View Abstract]
75. Zhong NS, Sun T, Zhuo C, D'Souza G, Lee SH, Lan NH, et al. Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial. Lancet Infect Dis. 2015 Feb. 15 (2):161-71. [View Abstract]
76. Low DE, File TM Jr, Eckburg PB, Talbot GH, David Friedland H, Lee J, et al. FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother. 2011 Apr. 66 Suppl 3:iii33-44. [View Abstract]
77. Chang SP, Lee HZ, Lai CC, Tang HJ. The efficacy and safety of nemonoxacin compared with levofloxacin in the treatment of community-acquired pneumonia: a systemic review and meta-analysis of randomized controlled trials. Infect Drug Resist. 2019. 12:433-438. [View Abstract]
78. U.S. National Library of Medicine. Study to Compare Delafloxacin to Moxifloxacin for the Treatment of Adults With Community-acquired Bacterial Pneumonia (DEFINE-CABP). Clinicaltrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT02679573?term=delafloxacin&cond=Pneumonia&rank=1. July 29, 2019; Accessed: September 2019.
79. Baxdela (delafloxacin) [package insert]. Lincolnshire, Il: Melinta Therapeutics, Inc. October 2019. Available at
80. Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018 Sep 6. 379 (10):913-923. [View Abstract]
81. Siemieniuk RA, Meade MO, Alonso-Coello P, Briel M, Evaniew N, Prasad M, et al. Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015 Oct 6. 163 (7):519-28. [View Abstract]
82. Restrepo MI, Anzueto A, Torres A. Corticosteroids for Severe Community-Acquired Pneumonia: Time to Change Clinical Practice. Ann Intern Med. 2015 Oct 6. 163 (7):560-1. [View Abstract]
83. An MM, Zou Z, Shen H, Gao PH, Cao YB, Jiang YY. Moxifloxacin monotherapy versus beta-lactam-based standard therapy for community-acquired pneumonia: a meta-analysis of randomised controlled trials. Int J Antimicrob Agents. 2010 Jul. 36(1):58-65. [View Abstract]
84. Anzueto A, Niederman MS, Pearle J, Restrepo MI, Heyder A, Choudhri SH. Community-Acquired Pneumonia Recovery in the Elderly (CAPRIE): efficacy and safety of moxifloxacin therapy versus that of levofloxacin therapy. Clin Infect Dis. 2006 Jan 1. 42(1):73-81. [View Abstract]
85. Davis SL, Delgado G Jr, McKinnon PS. Pharmacoeconomic considerations associated with the use of intravenous-to-oral moxifloxacin for community-acquired pneumonia. Clin Infect Dis. 2005 Jul 15. 41 Suppl 2:S136-43. [View Abstract]
86. Welte T, Petermann W, Schürmann D, Bauer TT, Reimnitz P,. Treatment with sequential intravenous or oral moxifloxacin was associated with faster clinical improvement than was standard therapy for hospitalized patients with community-acquired pneumonia who received initial parenteral therapy. Clin Infect Dis. 2005 Dec 15. 41(12):1697-705. [View Abstract]
87. Eurich DT, Sadowski CA, Simpson SH, Marrie TJ, Majumdar SR. Recurrent community-acquired pneumonia in patients starting acid-suppressing drugs. Am J Med. 2010 Jan. 123(1):47-53. [View Abstract]
88. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009 May 27. 301(20):2120-8. [View Abstract]
89. Dublin S, Walker RL, Jackson ML, Nelson JC, Weiss NS, Jackson LA. Use of proton pump inhibitors and H2 blockers and risk of pneumonia in older adults: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2010 Aug. 19(8):792-802. [View Abstract]
90. Restrepo MI, Mortensen EM, Anzueto A. Common medications that increase the risk for developing community-acquired pneumonia. Curr Opin Infect Dis. 2010 Apr. 23(2):145-51. [View Abstract]
91. Othman F, Crooks CJ, Card TR. Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study. BMJ. 2016 Nov 15. 355:i5813. [View Abstract]
92. Ro Y, Eun CS, Kim HS, Kim JY, Byun YJ, Yoo KS, et al. Risk of Clostridium difficile Infection with the Use of a Proton Pump Inhibitor for Stress Ulcer Prophylaxis in Critically Ill Patients. Gut Liver. 2016 Jul 15. 10 (4):581-6. [View Abstract]
93. Bjerre LM, Verheij TJ, Kochen MM. Antibiotics for community acquired pneumonia in adult outpatients. Cochrane Database Syst Rev. 2009 Oct 7. CD002109. [View Abstract]
94. Carrie AG, Kozyrskyj AL. Outpatient treatment of community-acquired pneumonia: evolving trends and a focus on fluoroquinolones. Can J Clin Pharmacol. 2006. 13(1):e102-11. [View Abstract]
95. Segreti J, House HR, Siegel RE. Principles of antibiotic treatment of community-acquired pneumonia in the outpatient setting. Am J Med. 2005 Jul. 118 Suppl 7A:21S-28S. [View Abstract]
96. Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015 Mar 19. 372 (12):1114-25. [View Abstract]
97. Kim DK, Bridges CB, Harriman KH, Advisory Committee on Immunization Practices (ACIP), ACIP Adult Immunization Work Group. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older--United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 Feb 5. 65 (4):88-90. [View Abstract]
98. Talbot HK, Zhu Y, Chen Q, Williams JV, Thompson MG, Griffin MR. Effectiveness of influenza vaccine for preventing laboratory-confirmed influenza hospitalizations in adults, 2011-2012 influenza season. Clin Infect Dis. 2013 Jun. 56 (12):1774-7. [View Abstract]
99. Phrommintikul A, Kuanprasert S, Wongcharoen W, Kanjanavanit R, Chaiwarith R, Sukonthasarn A. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. Eur Heart J. 2011 Jul. 32 (14):1730-5. [View Abstract]
100. Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A, et al. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA. 2013 Oct 23. 310 (16):1711-20. [View Abstract]
101. Powner J, Gallaher T, Colombo R, Baer S, Huber L, Kheda M, et al. Influenza vaccination reduced pneumococcal disease in incident dialysis patients. American Society of Nephrology. 2014.
102. CDC. Flu Vaccine and People With Allergies. CDC. Available at https://www.cdc.gov/flu/prevent/egg-allergies.htm. December 28, 2017; Accessed: September 2019.
103. Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR, Karron RA. Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 Influenza Season. MMWR Morb Mortal Wkly Rep. 2015 Aug 7. 64 (30):818-25. [View Abstract]
104. Kobayashi M, Bennett NM, Gierke R, Almendares O, Moore MR, Whitney CG, et al. Intervals Between PCV13 and PPSV23 Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2015 Sep 4. 64 (34):944-7. [View Abstract]
105. Cao B, Huang Y, She DY, Cheng QJ, Fan H, Tian XL, et al. Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association. Clin Respir J. 2018 Apr. 12 (4):1320-1360. [View Abstract]
106. Mortensen EM, Halm EA, Pugh MJ, Copeland LA, Metersky M, Fine MJ, et al. Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia. JAMA. 2014 Jun 4. 311(21):2199-208. [View Abstract]
107. Busko M. Azithromycin Benefits Outweigh MI Risks in Older Pneumonia Patients. Medscape Medical News. Available at http://www.medscape.com/viewarticle/826175. Accessed: June 9, 2014.
108. Cunha BA. Elevated Serum Transaminases in Mycoplasma pneumoniae Pneumonia. Clin Microbiol Infect. 2005. 11:1051-1054.
109. Cunha BA. Hypophosphatemia: Diagnostic Significance in Legionnaires' Disease. Am J Med. 2006. 119:5-6.
110. Bradley, JS et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: Clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011. 53:e25-e76.
111. Boselli E, Breilh D, Rimmelé T, Djabarouti S, Saux MC, Chassard D. Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia. Crit Care Med. 2005 Jan. 33(1):104-9. [View Abstract]
112. Mokabberi R, Haftbaradaran A, Ravakhah K. Doxycycline vs. levofloxacin in the treatment of community-acquired pneumonia. J Clin Pharm Ther. 2010 Apr. 35(2):195-200. [View Abstract]
113. Noreddin AM, Elkhatib WF. Levofloxacin in the treatment of community-acquired pneumonia. Expert Rev Anti Infect Ther. 2010 May. 8(5):505-14. [View Abstract]
114. Cunha BA (ed). Pneumonia Essentials. 3rd Ed. Sudbury, MA: Jones & Bartlett; 2010.
115. Boulware DR, Daley CL, Merrifield C, Hopewell PC, Janoff EN. Rapid diagnosis of pneumococcal pneumonia among HIV-infected adults with urine antigen detection. J Infect. 2007 Oct. 55(4):300-9. [View Abstract]
116. Westley BP, Chan PA. Questions remain regarding mandatory use of macrolides in community-acquired pneumonia. Intensive Care Med. 2010 Oct. 36(10):1787; author reply 1789-90. [View Abstract]
117. Iannini PB, Paladino JA, Lavin B, Singer ME, Schentag JJ. A case series of macrolide treatment failures in community acquired pneumonia. J Chemother. 2007 Oct. 19(5):536-45. [View Abstract]
118. Lodise TP, Kwa A, Cosler L, Gupta R, Smith RP. Comparison of beta-lactam and macrolide combination therapy versus fluoroquinolone monotherapy in hospitalized Veterans Affairs patients with community-acquired pneumonia. Antimicrob Agents Chemother. 2007 Nov. 51(11):3977-82. [View Abstract]
119. Johnstone J, Marrie TJ, Eurich DT, Majumdar SR. Effect of pneumococcal vaccination in hospitalized adults with community-acquired pneumonia. Arch Intern Med. 2007 Oct 8. 167(18):1938-43. [View Abstract]
120. Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, et al. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged =65 Years: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014 Sep 19. 63(37):822-5. [View Abstract]
121. Bonten M, Bolkenbaas M, Huijts S, et al. Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA). Abstract no. 0541. Pneumonia 2014;3:95. Available at https://pneumonia.org.au/public/journals/22/PublicFolder/ABSTRACTBOOKMASTERforwebupdated20-3-14.pdf
122. Boggs W. Narrow-Spectrum Antibiotics Effective as Empiric Therapy for Pediatric Pneumonia. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/818253. Accessed: January 5, 2014.
123. Queen MA, Myers AL, Hall M, Shah SS, Williams DJ, Auger KA, et al. Comparative effectiveness of empiric antibiotics for community-acquired pneumonia. Pediatrics. 2014 Jan. 133(1):e23-9. [View Abstract]
124. Restrepo MI, Mortensen EM, Pugh JA, Anzueto A. COPD is associated with increased mortality in patients with community-acquired pneumonia. Eur Respir J. 2006 Aug. 28(2):346-51. [View Abstract]
125. Athlin S, Lidman C, Lundqvist A, Naucler P, Nilsson AC, Spindler C, et al. Management of community-acquired pneumonia in immunocompetent adults: updated Swedish guidelines 2017. Infect Dis (Lond). 2018 Apr. 50 (4):247-272. [View Abstract]