Advertisement

Guidelines for the Evaluation and Treatment of Pneumonia

      Keywords

      Key points

      • Pneumonia is a common respiratory infection and warrants careful consideration of antibiotic initiation and choice, along with knowledge of local antibiotic resistance patterns.
      • Community-acquired pneumonia afflicts all age groups and although not always bacterial in origin, is clinically versatile, depending on its cause.
      • Nonresolving pneumonia may be because of less common pathogens, or feature other conditions, and requires more detailed investigation.
      • Pediatric pneumonia is also common, and first-line treatment is still amoxicillin, followed closely by cephalosporins or macrolides.
      • Other categories of pneumonia, including mechanically induced (ventilator) or travel/geriatric pneumonia, benefit from astute clinical acumen, proper history and physical examination, and knowledge of microbial causes.

      Introduction

      Pneumonia is a leading cause of hospitalization among both adults and children in the United States, accounting for more than 800,000 hospitalizations and more than 400,000 emergency department visits in 2014.
      • McDermott K.W.
      • Elixhauser A.
      • Sun R.
      Trends in hospital inpatient stays in the United States, 2005-2014. HCUP statistical brief #225.

      Rui P, Kang K. National Hospital Ambulatory Medical Care Survey: 2014 emergency department summary tables. Available at: http://www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2014_ed_web_tables.pdf. Accessed January 16, 2018.

      It is among the most expensive conditions treated in US hospitals with national aggregate costs of $9.5 billion in 2013.
      • Torio C.
      • Moore B.
      National inpatient hospital costs: the most expensive conditions by payer, 2013. HCUP statistical brief #204.
      A causal pathogen is often not identified. A 2015 prospective, multi-center study by the Centers for Disease Control and Prevention identified a responsible pathogen in only 38% of cases of community-acquired pneumonia (CAP) in adults requiring hospitalization.
      • Jain S.
      • Self W.H.
      • Wunderink R.G.
      • et al.
      Community-acquired pneumonia requiring hospitalization among U.S. adults.
      CAP is an infection of the lung parenchyma that is acquired outside of hospitals or extended-care facilities.
      • Cisneros E.D.
      • Lazarte S.M.
      General infectious diseases.
      Viral pathogens were identified in 27% of cases and bacterial pathogens in 14% of cases.
      • Cisneros E.D.
      • Lazarte S.M.
      General infectious diseases.
      In adults of all ages, human rhinovirus and influenza were the most frequently identified viruses.
      • Cisneros E.D.
      • Lazarte S.M.
      General infectious diseases.
      Streptococcus pneumoniae is the most common causal bacterium. Staphylococcus aureus and Enterobacteriaceae were significantly more common among patients requiring intensive care unit (ICU) level care.
      • Jain S.
      • Self W.H.
      • Wunderink R.G.
      • et al.
      Community-acquired pneumonia requiring hospitalization among U.S. adults.
      Other bacteria identified in CAP include Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Haemophilus influenzae.
      • Cisneros E.D.
      • Lazarte S.M.
      General infectious diseases.
      Less common bacterial causes include Mycobacterium tuberculosis, Legionella sp, and Pseudomonas aeruginosa. These and other bacteria may be considered more likely in patients with certain risk factors (Table 1).
      • Kaysin A.
      • Viera A.J.
      Community- acquired pneumonia in adults: diagnosis and management.
      Table 1Risk factors and infectious causes in community-acquired pneumonia
      Adapted from Kaysin A, Viera AJ. Community-acquired pneumonia in adults: diagnosis and management. Am Fam Physician 2016;94(9):699; with permission.
      Risk FactorInfectious
      Agricultural animalsCoxiella burnetii (Q fever)
      AIDSAspergillus and Cryptococcus species, Histoplasma capsulatum, Haemophilus influenzae, Nocardia species, nontuberculous mycobacteria, Pneumocystis jiroveci
      Alcoholism (aspiration)Anaerobic oral flora, Klebsiella pneumoniae, Mycobacterium tuberculosis, Streptococcus pneumoniae
      Avian fecal matterH. capsulatum
      Chronic obstructive pulmonary diseaseChlamydophila pneumoniae, H. influenzae, Legionella species, Moraxella catarrhalis, Pseudomonas aeruginosa or other gram-negative rods, S. pneumoniae
      HIV infectionH. influenzae, M. tuberculosis, S. pneumoniae
      Hotel or cruise ship travel (recent)Legionella species
      InfluenzaH. influenzae, influenza and other respiratory viruses, S. pneumoniae, Staphylococcus aureus (including MRSA)
      Intravenous drug useAnaerobes, M. tuberculosis, S aureus (including MRSA), S. pneumoniae
      Pulmonary abscessAnaerobic oral flora, M. tuberculosis, nontuberculous mycobacteria, S. aureus (including MRSA)
      Travel (national/international)Blastomyces dermatitidis, Coccidioides species, Hantavirus species

      Middle East respiratory syndrome, Avian influenza, inter alia
      Abbreviations: AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus; MRSA, methicillin-resistant staphylococcus aureus.

      Diagnosis

      A diagnosis of pneumonia should be considered in patients presenting with acute onset fever or chills and cough. The cough may be described as productive. Additional symptoms frequently seen include fatigue, anorexia, and pleuritic chest pain. Important components of a history include recent travel, history of underlying lung disease, and smoking history.
      • Jain S.
      • Self W.H.
      • Wunderink R.G.
      • et al.
      Community-acquired pneumonia requiring hospitalization among U.S. adults.
      • Kaysin A.
      • Viera A.J.
      Community- acquired pneumonia in adults: diagnosis and management.
      A study by Diehr and colleagues
      • Diehr P.
      • Wood R.W.
      • Bushyhead J.
      • et al.
      Prediction of pneumonia in outpatients with acute cough: a statistical approach.
      found that history of alcoholism or bloody sputum have relative risk of 1, so the presence of these findings is not predictive of pneumonia. Physical examination findings frequently appreciated in patients with pneumonia include decreased breath sounds, rales, tactile fremitus, and crackles.
      • Jain S.
      • Self W.H.
      • Wunderink R.G.
      • et al.
      Community-acquired pneumonia requiring hospitalization among U.S. adults.
      • Simel D.L.
      • Metlay J.P.
      Pneumonia, adult, community-acquired.
      Tachypnea and hypotension are more worrisome symptoms that may also be seen and require urgent evaluation.
      • Jain S.
      • Self W.H.
      • Wunderink R.G.
      • et al.
      Community-acquired pneumonia requiring hospitalization among U.S. adults.
      It is imperative to maintain a high level of suspicion in immunocompromised or elderly and nursing home patients, because they frequently display fewer overt symptoms of pneumonia when compared with the general population.
      • Simel D.L.
      • Metlay J.P.
      Pneumonia, adult, community-acquired.
      • Casey C.
      • Fullerton M.
      • Somerville N.
      Common questions about pneumonia in nursing home residents.
      No individual component of the history or physical examination is useful in diagnosing pneumonia, but the presence of multiple findings is required (Table 2). In adults presenting with acute cough, the baseline probability of pneumonia is only 5%. Absence of any vital sign abnormality (blood pressure, heart rate, respiratory rate) reduces the predicted probability of pneumonia to 1%.
      • Simel D.L.
      • Metlay J.P.
      Pneumonia, adult, community-acquired.
      A chest radiograph should be ordered for any patient with abnormal vital signs defined as temperature higher than 100°F, heart rate higher than 100 bpm, or respiratory rate higher than 20 bpm. Imaging should also be obtained for physical examination abnormalities of crackles or decreased breath sounds in a patient without asthma.
      • Ebell M.H.
      Predicting pneumonia in adults with respiratory illness.
      Infectious Disease Society of America 2016 Guidelines recommend imaging with a demonstrable infiltrate to confirm the diagnosis of pneumonia and to exclude other causes of cough and fever such as acute bronchitis.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      Although X-ray imaging is a mainstay of diagnosis of pneumonia, the British Thoracic Society recommends the entire clinical picture should be considered when making a decision to treat.
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
      A systematic review found that among patients who are sick enough to be admitted with a clinical diagnosis of CAP but have a normal initial chest radiograph, approximately 1 in 10 will develop radiographic evidence of pneumonia within 72 hours.
      • Simel D.L.
      • Metlay J.P.
      Pneumonia, adult, community-acquired.
      In such cases, it is appropriate to treat the patient empirically for pneumonia and repeat imaging in 24 to 48 hours.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      Community resources and access to imaging may also affect decision to treat without imaging.
      Table 2Predictors of adult pneumonia
      Adapted from Simel DL, Rennie D. Pneumonia, adult, community-acquired. In: Simel DL, Rennie D, editors. The rational clinical examination: evidence-based clinical diagnosis. New York: McGraw-Hill; 2009; with permission.
      ScoreLikelihood Ratio
      ≥314
      ≥15
      ≥−11.5
      <−10.22
      Add or subtract points as follows: rhinorrhea = −2, sore throat = −1, night sweats = 1, myalgias = 1, sputum all day = 1, respiratory rate >25/min = 2, temperature ≥37.8°C (100°F) = 2.
      Routine blood and sputum culture testing is costly and often low-yield.
      • Gupta D.
      • Agarwal R.
      • Aggarwal A.N.
      • et al.
      Guidelines for diagnosis and management of community- and hospital-acquired pneumonia in adults: joint ICS/NCCP(I) recommendations.
      However, more extensive diagnostic testing should be considered in patients who are at risk for infection with unusual pathogens, who are not responding to treatment, or when additional testing is likely to change antibiotic management (Table 3).
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
      Table 3Indications for further testing
      Adapted from Mandell L, Wunderink R, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Supplement_2), S40; with permission.
      IndicationBlood CultureSputum CultureLegionella UATPneumococcal UATOther
      ICU admissionXXXXx
      Endotracheal aspirate if intubated, bronchoscopic alveolar lavage, as needed.
      Failure of outpatient antibiotic therapyxxX
      Cavitary infiltratesXXx
      Fungal and tuberculosis cultures.
      Leukopeniaxx
      Alcohol abuse (current)xXxx
      Liver diseasexx
      Lung diseasex
      Aspleniaxx
      Travel within past 2 wkxx
      See Table 1.
      Positive Legionella UAT resultsxNA
      Positive pneumococcal UAT resultxxNA
      Pleural effusionxxxxx
      Thoracentesis and pleural fluid cultures.
      Abbreviations: NA, not applicable; UAT, urinary antigen test.
      a Endotracheal aspirate if intubated, bronchoscopic alveolar lavage, as needed.
      b Fungal and tuberculosis cultures.
      c See Table 1.
      d Thoracentesis and pleural fluid cultures.
      It is reasonable to consider respiratory viral polymerase chain reaction (PCR) to determine viral causes of symptoms, so that inappropriate antibiotic use can be limited. Additional testing for M. tuberculosis should be considered in a patient presenting with persistent cough, particularly in the setting of weight loss, malaise, night sweats, or hemoptysis. Additional risk factors for tuberculosis (TB) include immigration from an endemic country, residing in a homeless shelter, intravenous drug use, or human immunodeficiency virus (HIV) infection. Persons who work with people at high risk for TB infection are also considered high risk.
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.

      Tuberculosis (TB) | CDC. Cdcgov. 2018. Available at: https://www.cdc.gov/tb/default.htm. Accessed February 24, 2018.

      Treatment

      Most cases of pneumonia can be managed in the outpatient setting. Several severity assessment tools have been developed to help determine appropriate treatment settings. The Pneumonia Severity Index (PSI) considers 20 variables to stratify patients into 1 of 5 risk categories (I–V) based on risk of death within 30 days.
      • Chalmers J.
      • Singanayagam A.
      • Akram A.
      • et al.
      Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis.
      Given the number of parameters required, it is not frequently used in general practice. The CURB65 assessment tool was introduced in 2003 by the British Thoracic Society.
      • Lim W.S.
      • van der Eerden M.M.
      • Laing R.
      • et al.
      Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study.
      Similar to the PSI, it calculates risk of 30-day mortality, but instead only uses 5 variables (confusion, urea, respiratory rate, blood pressure, and age >65), with one point awarded for each if present, allowing for greater ease of use.
      • Chalmers J.
      • Singanayagam A.
      • Akram A.
      • et al.
      Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis.
      • Lim W.S.
      • van der Eerden M.M.
      • Laing R.
      • et al.
      Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study.
      The CRB65 can be calculated without blood urea and thus is useful in the outpatient setting. A recent systematic review and meta-analysis found no significant difference in test performance when comparing the 3 severity tools.
      • Chalmers J.
      • Singanayagam A.
      • Akram A.
      • et al.
      Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis.
      It was noted that the PSI negative likelihood ratio suggests it may be superior in identifying low-risk patients, and the CURB65 and CRB65 may be superior in identifying high-risk patients.
      • Chalmers J.
      • Singanayagam A.
      • Akram A.
      • et al.
      Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis.
      A CURB65 or CRB65 score of 0 or 1 demonstrates low risk of mortality and suggests a patient can be managed in the outpatient setting. A score of 3 or higher should warrant hospital admission. It is always appropriate to consider a patient’s social circumstances and treatment wishes when making treatment decisions
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
      • Lim W.S.
      • van der Eerden M.M.
      • Laing R.
      • et al.
      Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study.
      (Fig. 1; CURB65 score
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
      ).
      Figure thumbnail gr1
      Fig. 1CURB65 score.
      (Adapted from Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009;64(suppl 3):iii29; with permission.)
      When available, treatment of CAP should be guided by local resistance patterns. In previously healthy patients who are appropriate for outpatient treatment, recommended first-line treatment is with a macrolide antibiotic such as azithromycin targeting the most common causal pathogen S. pneumoniae. Doxycycline is an alternative option. Patients with comorbidities such as diabetes; chronic heart, lung, renal, or liver disease; alcoholism; asplenia; impaired immune system; or recent antibiotic use within the last 3 months have an increased risk for drug-resistant S pneumoniae. As such, a respiratory fluoroquinolone or β-lactam plus a macrolide is recommended (Table 4).
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      Table 4Outpatient treatment of community-acquired pneumonia
      Adapted from Mandell L, Wunderink R, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Supplement 2):S45.
      Presence of ComorbiditiesAntibiotic Choice
      NOMacrolide or doxycycline
      YESFluoroquinolone or beta-lactam + macrolide (doxycycline is an alternative for macrolide)
      Comorbidities: chronic heart; lung, liver, kidney disease; diabetes; cancer; impaired immune system; alcoholism; asplenia; recent use of antibiotics in previous 3 mo; and risk for multidrug-resistant S. pneumoniae.
      A 2014 Cochrane review found no significant differences in efficacy between antibiotic regimens, although there were differences in adverse effects when comparing antibiotics within a single class.
      • Pakhale S.
      • Mulpuru S.
      • Verheij T.J.M.
      • et al.
      Antibiotics for community-acquired pneumonia in adult outpatients.
      Patients appropriate for inpatient non-ICU treatment should also be treated with a respiratory fluoroquinolone or macrolide with β-lactam. Patients should be treated for a minimum of 5 days and should be clinically stable with resolving symptoms before treatment is discontinued.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      • Uranga A.
      • España P.
      • Bilbao A.
      • et al.
      Duration of antibiotic treatment in community-acquired pneumonia.
      Patients with high severity of infection or with extrapulmonary manifestations may benefit from longer duration of therapy, such as 7 to 10 days or until improving.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
      In recent years, there has been emerging data supporting the use of adjunctive corticosteroids in the inpatient treatment of CAP. As this is an area of research, multiple recent systematic reviews and meta-analyses have been published, some with conflicting findings. A 2011 Cochrane review that included relevant CAP studies through the year 2010 showed that corticosteroid use accelerates time to symptom resolution and clinical stability, with infrequent adverse effects.
      • Chen Y.
      • Li K.
      • Pu H.
      • et al.
      Corticosteroids for pneumonia.
      Similarly, a 2015 systematic review by Siemieniuk and colleagues
      • Siemieniuk R.
      • Alonso-Coello P.
      • Guyatt G.
      Corticosteroid therapy for patients hospitalized with community-acquired pneumonia.
      included studies from 2011 through mid-2015. Their analysis of 13 randomized controlled trials found significantly decreased mortality in severe pneumonia, decreased need for mechanical ventilation, decreased occurrence of acute respiratory distress syndrome, decreased time to clinical stability, and shorter duration of hospitalization.
      • Siemieniuk R.
      • Alonso-Coello P.
      • Guyatt G.
      Corticosteroid therapy for patients hospitalized with community-acquired pneumonia.
      Hyperglycemia requiring treatment occurred more frequently in patients treated with corticosteroids.
      • Siemieniuk R.
      • Alonso-Coello P.
      • Guyatt G.
      Corticosteroid therapy for patients hospitalized with community-acquired pneumonia.
      • Feldman C.
      • Anderson R.
      Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.
      The most recent IDSA and BTS guidelines do not make recommendations regarding the routine use of adjunctive corticosteroid for CAP.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
      Given the variations in dose and route of administration, an optimal agent and dose is unknown. Further research is needed to determine steroid dosing and duration, as well as what patient populations are most likely to benefit from its use.
      • Siemieniuk R.
      • Alonso-Coello P.
      • Guyatt G.
      Corticosteroid therapy for patients hospitalized with community-acquired pneumonia.
      • Feldman C.
      • Anderson R.
      Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.
      There are a large number of studies assessing the role of the infection biomarker procalcitonin in diagnosis and monitoring of patients with bacterial infections.
      • Sager R.
      • Kutz A.
      • Mueller B.
      • et al.
      Procalcitonin-guided diagnosis and antibiotic stewardship revisited.
      A Cochrane 2017 meta-analysis in the primary care setting concluded that the use of procalcitonin to guide initiation and duration of antibiotic treatment results in lower risks of mortality, lower antibiotic consumption, and lower risk for antibiotic-related side effects.
      • Schuetz P.
      • Wirz Y.
      • Sager R.
      • et al.
      Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.
      Procalcitonin values too low or too high usually exclude bacterial infection, but not always.
      • Tan L.
      • Louie S.
      Unresolved Acute Pneumonia: a “BAD OMEN”.
      Per practitioner discretion and, depending on patient complexity and other comorbidities, a follow-up appointment after successful management in the primary care setting may be arranged. At this appointment, repeat X-ray imaging to confirm resolution of pneumonia is not indicated if the patient seems clinically well. In patients with persistence of symptoms or who have a high risk of lung cancer (age > 50, >30 pack year smoking history), repeat X-ray imaging or low-dose computerized tomography (CT) scan to screen for lung cancer can be considered.
      • Lim W.
      • Baudouin S.
      • George R.
      • et al.
      BTS guidelines for the management of community acquired pneumonia in adults: update 2009.

      Prevention

      In the United States, the pneumococcal conjugate vaccine (PCV13 or Prevnar-13) is recommended for all babies and children younger than 2 years, all adults aged 65 years or older, as well as children and adults aged 2 years through 64 years who are at increased risk for pneumococcal disease due to certain medical conditions.
      • Tan L.
      • Louie S.
      Unresolved Acute Pneumonia: a “BAD OMEN”.
      The pneumococcal conjugate vaccine has been shown to have an observed 46% reduction in vaccine-type pneumococcal CAP, persisting for at least 4 years after receiving the vaccine.

      Cdc.gov. Pneumococcal vaccination | what you should know | CDC. [online]. 2017. Available at: https://www.cdc.gov/vaccines/vpd/pneumo/public/index.html. Accessed December 14, 2017.

      • Bonten M.
      • Huijts S.M.
      • Bolkenbaas M.
      • et al.
      Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.
      The pneumococcal polysaccharide vaccine (PPSV23 or Pneumovax 23) is recommended for all adults aged 65 years or older, all cigarette smokers aged 19 to 64 years, as well as children and adults aged 2 to 64 years with certain medical conditions.
      • Centers for Disease Control and Prevention
      Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23).
      A 2013 Cochrane review found that the polysaccharide vaccine is effective in preventing invasive pneumococcal disease in healthy adults. Vaccine efficacy was, however, poorer in adults with chronic illnesses.
      • Moberley S.
      • Holden J.
      • Tatham D.P.
      • et al.
      Vaccines for preventing pneumococcal infection in adults.

      Nonresolving pneumonia

      Pneumonia is considered “nonresolving” if there is an inadequate clinical response despite antibiotic treatment.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      The incidence of treatment failure is 6% to 15% and is associated with a 5-fold increase in mortality.
      • Sialer S.
      • Liapikou A.
      • Torres A.
      What is the best approach to the nonresponding patient with community-acquired pneumonia?.
      IDSA broadly classifies nonresponse into 2 different groups: (1) progressive pneumonia characterized by clinical deterioration and (2) persistent pneumonia with absence or delay of clinical stability.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      Progressive pneumonia with deterioration is characterized by respiratory failure and/or septic shock and typically occurs within 72 hours. Persistent pneumonia with absent or delayed response is typically considered after a time period of 72 hours, because this is often regarded as the median time required for clinical stability.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      • Sialer S.
      • Liapikou A.
      • Torres A.
      What is the best approach to the nonresponding patient with community-acquired pneumonia?.
      Concern for nonresponse in a patient with pneumonia should initiate a systematic evaluation of possible causes. Host factors that may explain poor response should be considered, including high initial severity score, risk factors for infection with unusual organisms, underlying comorbidities, or risk factors for multi–drug-resistant pathogens (Table 5).
      • Tan L.
      • Louie S.
      Unresolved Acute Pneumonia: a “BAD OMEN”.
      In areas with high prevalence of HIV or TB, testing is recommended.
      • Trimble A.
      • Moffat V.
      • Collins A.
      Pulmonary infections in the returned traveler.
      Results of initial microbiological tests such as blood or sputum cultures should be reviewed, including any sensitivity data. Repeat blood cultures should be obtained in the setting of clinical deterioration. Additional laboratory testing for S. pneumonia and Legionella pneumophila via urine antigen testing may be performed, because they may remain positive for days after initiating antibiotic treatment. Additional imaging such as chest CT may be beneficial for assessing interval progression or improvement or identifying pleural effusions, lung abscesses, or pulmonary embolism. If pleural effusions are identified in a patient with treatment failure, thoracentesis should be performed to evaluate for empyema. In select patients, bronchoscopy with protected bronchial sampling or bronchoalveolar lavage (BAL) may be beneficial to provide diagnostic information for infectious causes and noninfectious mimics, such as pulmonary eosinophilia, drug-induced pneumonitis, sarcoidosis, or pulmonary fibrosis.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      • Sialer S.
      • Liapikou A.
      • Torres A.
      What is the best approach to the nonresponding patient with community-acquired pneumonia?.
      Primary or metastatic neoplastic lesions obstructing the bronchus may cause accumulation of secretions distal to the obstruction, predisposing to infection. Both Hodgkin and non-Hodgkin lymphoma can present with lung involvement, with typical radiographic findings of hilar or mediastinal adenopathy, but may also have a presenting pattern that suggests infection.
      • Black A.
      Non-infectious mimics of community-acquired pneumonia.
      Table 5BAD OMEN (nonresolving pneumonia)
      Adapted from Tan L, Louie S. Unresolved acute pneumonia: a “BAD OMEN”. Consultant 2017;57(8):502; with permission.
      Disease/Risk Factor MnemonicListing of Diseases/Conditions/Risk Factors
      BBronchiolitis obliterans/Bronchiectasis/Influenza B
      AAge >60/Aspiration/Anaerobic infection/Abscess/Influenza A/Atypical pathogens (eg, Legionella, Mycoplasma, hMPV, chlamydia)
      DDrug-resistant pneumonia from S. Pneumoniae, gram-negative bacteria, MRSA, ESBL/Drug-induced pneumonitis (eg, amiodarone, MTX, nitrofurantoin, cancer biologics)/Delayed resolution from corticosteroids
      OOpportunistic pathogens (eg, Fungi, mold, Pneumocystis Jiroveci); anaerobic bacteria. Consider HIV testing.
      MMisdiagnosis (fungal infections, sarcoidosis, TB)
      EEmbolism/Empyema/Eosinophilic pneumonia
      NNeoplasm/Nosocomial bacterial pneumonia
      Abbreviations: ESBL, extended-spectrum beta-lactamase organisms; hMPV, human metapneumovirus; MTX, methotrexate.

      Pneumonia in the elderly

      Elderly patients with pneumonia may not exhibit typical symptoms or physical examination findings seen in younger adults, such as pleuritic chest pain, cough, fever, and leukocytosis.
      • Faverio P.
      • Aliberti S.
      • Bellelli G.
      • et al.
      The management of community-acquired pneumonia in the elderly.
      Signs and symptoms more frequently seen in older adults include falls, decreased appetite, or functional impairment.
      • Faverio P.
      • Aliberti S.
      • Bellelli G.
      • et al.
      The management of community-acquired pneumonia in the elderly.
      A change in mental status should prompt evaluation for an infectious cause.
      • Casey C.
      • Fullerton M.
      • Somerville N.
      Common questions about pneumonia in nursing home residents.
      • Mandell L.
      • Wunderink R.
      • Anzueto A.
      • et al.
      Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
      As with any adult, risk factors for atypical or drug-resistant pathogens should guide treatment. Elderly patients with history of stroke or known dysphagia are at an increased risk for aspiration pneumonia. Residents of nursing homes or long-term care facilities are at an increased risk for methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant (MDR) pathogens.
      • Faverio P.
      • Aliberti S.
      • Bellelli G.
      • et al.
      The management of community-acquired pneumonia in the elderly.

      Travel

      Evaluation of a returned traveler should include the following: appropriate history covering the travel itinerary (location and activities), onset of illness related to travel, vaccines or prophylaxis received, diet, sexual history, and exposure to animals.
      • Trimble A.
      • Moffat V.
      • Collins A.
      Pulmonary infections in the returned traveler.
      • Centers for Disease Control and Prevention
      CDC yellow book 2018: health information for international travel.
      Respiratory tract infections are among the most common health care complaints affecting returned travelers and are diagnosed in up to 24% of returned patients with fever.
      • Trimble A.
      • Moffat V.
      • Collins A.
      Pulmonary infections in the returned traveler.
      • Meltzer E.
      • Schwartz E.
      Travel-related respiratory infections.
      Although upper respiratory tract infections are more common, the severity and possible mortality associated with lower respiratory tract infections such as pneumonia make it a must-not-miss diagnosis in the returned traveler. As in the United States, S pneumoniae, H. influenzae, and S. aureus are the dominant pneumonia isolates in developing countries. It must be considered that bacterial resistance patterns from different countries may differ in these otherwise commonplace bacteria.
      • Meltzer E.
      • Schwartz E.
      Travel-related respiratory infections.
      Respiratory symptoms occur in up to half of patients with malaria, and the presentation may seem similar to that of pneumonia. Thus, in a patient returning from a malaria-endemic area, blood smear testing for malaria should be performed.

      Fairley JK. General approach to the returned traveler. In: Chapter 5: post-travel evaluation. Centers for disease control and prevention. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/post-travel-evaluation/general-approach-to-the-returned-traveler. Accessed February 26, 2018.

      Increased time spent at hotels or on cruise ships in a patient presenting with symptoms of pneumonia should increase suspicion for Legionella.
      • Trimble A.
      • Moffat V.
      • Collins A.
      Pulmonary infections in the returned traveler.
      Travelers returning from East and Southeast Asia, as well as Australia, with a severe pneumonia may have been exposed to Burkholderia pseudomallei—the causative agent of melioidosis, which can cause severe necrotizing pneumonia and has 14% to 40% mortality despite appropriate antibiotic therapy.
      • Trimble A.
      • Moffat V.
      • Collins A.
      Pulmonary infections in the returned traveler.
      Severe pneumonia may also be because of viruses such as influenza, Middle Eastern respiratory syndrome, or hantavirus. A returned traveler with pneumonia with eosinophilia should raise suspicion for helminth infection.
      • Trimble A.
      • Moffat V.
      • Collins A.
      Pulmonary infections in the returned traveler.
      • Meltzer E.
      • Schwartz E.
      Travel-related respiratory infections.
      Histoplasma capsulatum is a dimorphic fungus that is relatively common in North, Central, and South America and given its growth in bird and bat droppings is associated with activities such as cave exploration. Coccidioides immitis is endemic in the southwest United States and northern Mexico, as well as smaller areas in Central America. It is spread through inhalation of spores found in the soil. Fungal infection with H. capsulatum and C immitis are often asymptomatic but may also present as a flulike illness with fever, malaise, and dry cough 1 to 3 weeks after exposure.
      • Meltzer E.
      • Schwartz E.
      Travel-related respiratory infections.
      • Segel M.J.
      • Schwartz E.
      Histoplasmosis and other endemic fungal infections.

      Ventilator-Associated Pneumonia

      Ventilator-associated pneumonia (VAP) is a type of pneumonia that occurs in patients who have been intubated or mechanically ventilated by means of a tracheostomy for at least 48 hours.
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      • File T.M.
      Treatment of hospital-acquired and ventilator-associated pneumonia in adults.
      Mechanical ventilation modifies the oropharyngeal and tracheal environment, allowing oral and gastric secretions to enter the lower airways.
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      It is this change in lower respiratory tract bacterial flora that precipitates the beginning of pneumonia.
      VAP is common. Approximately 30% of patients who receive mechanical ventilation will develop VAP.
      • Cook D.J.
      • Walter S.D.
      • Cook R.J.
      • et al.
      Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients.

      Diagnostic criteria

      VAP should be suspected when signs of pulmonary infection (fever, purulent secretions, leukocytosis) and radiologic evidence (air bronchograms, infiltrates) are present; bacteriologic confirmation usually follows.
      • Fabregas N.
      • Ewig S.
      • Torres A.
      • et al.
      Clinical diagnosis of ventilator-associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies.
      Sensitivity and specificity of the diagnostic criteria discussed earlier are 69% and 75%, respectively.
      • Fabregas N.
      • Ewig S.
      • Torres A.
      • et al.
      Clinical diagnosis of ventilator-associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies.
      Other useful diagnostic criteria have been developed, incorporating additional symptoms and similar signs and laboratory/radiologic criteria.
      • Horan T.
      • Gaynes R.
      Survillence of nosocomial infection.
      Once VAP is clinically suspected, early empirical treatment is favored. Delaying treatment and/or not appropriately covering for the likely microbial culprit are both associated with higher morbidity and mortality.
      • El Kuti
      • Patel A.A.
      • Coleman C.I.
      Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associate pneumonia and blood stream infection: a meta-analysis.
      • Muscedere J.G.
      • Shorr A.F.
      • Jiang X.
      • et al.
      The adequacy of timely empiric antibiotic therapy for ventilator-associate pneumonia: an important determinant of outcome.
      • Paul M.
      • Shani V.
      • Muchtar E.
      • et al.
      Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis.
      • Swanson J.M.
      • Wells D.L.
      Empirical antibiotic therapy for ventilator-associated pneumonia.

      Microbiology

      Microbial organisms associated with VAP have been identified (Table 6). Early versus late-onset VAP organisms have also been documented.
      • Thakuria B.
      • Singh P.
      • Agrawal S.
      • et al.
      Profile of infective microorganisms causing ventilator-associated pneumonia: A clinical study from resource limited intensive care unit.
      • Rello J.
      • Torres A.
      Microbial causes of ventilator-associated pneumonia.
      Acinetobacter, citrobacter, pseudomonas, and klebsiella are the most predominant late-onset organisms, warranting more aggressive antibacterial intervention.
      • Rello J.
      • Torres A.
      Microbial causes of ventilator-associated pneumonia.
      Table 6Bacterial distribution in ventilator-associated pneumonia
      Adapted from Thakuria B, Singh P, Agrawal S, et al. Profile of infective microorganisms causing ventilator-associated pneumonia: a clinical study from resource limited intensive care unit. J Anaesthesiol Clin Pharmacol 2013;29(3):363; with permission.
      Bacterial OrganismPercentage
      Citrobacter freundii53
      Klebsiella pneumoniae13
      Staphylococcus aureus9.5
      Acinetobacter baumannii7.5
      Pseudomonas aeruginosa3.8
      P. aeruginosa + C. freundii3.8
      Coagulase-negative Staphylococci1.9
      Escherichia coli1.9
      Morganella morganii1.9
      Proteus vulgaris1.9
      P. aeruginosa + K. pneumoniae1.9

      Diagnostic testing

      Bacterial confirmation usually requires secretion sampling, either via bronchoscopic or via nonbronchoscopic methods. Obtaining pleural fluid, when present, under ultrasound guidance, is recommended.
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      Endotracheal aspirates are easily retrieved but have a high false-positive rate in ICU patients due to airway colonization.
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      Bronchoscopic retrieval of distal airway specimens via BAL or protected-specimen brush techniques is the best, but requires a trained bronchoscopist.
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.

      Antibiotic treatment

      Selection of antibiotics is typically done empirically and based on whether the patient has any risk factors for MDR pathogens (Table 7) and whether onset of VAP is early (defined as within first 4 days of being in the ICU) or late (5 days or later).
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      • File T.M.
      Treatment of hospital-acquired and ventilator-associated pneumonia in adults.
      • Kalil A.C.
      • Metersky M.L.
      • Klompas M.
      • et al.
      Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.
      Empirical treatment should also be determined as a result of knowledge of local distribution of pathogens and their antimicrobial susceptibility patterns.
      • Beardsley J.R.
      • Williamson J.C.
      • Johnson J.W.
      • et al.
      Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.
      Early-onset VAP without MDR risk factors typically should be prescribed one of the following antibiotic options
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      :
      • Ceftriaxone
      • Fluoroquinolone
      • Ampicillin-sulbactam
      • Ertapenem
      Table 7Risk factors for multidrug-resistant ventilator-associated pneumonia
      Adapted from Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:e61; with permission.
      Risk Factors for MDR PathogensRisk Factors for MDR Pseudomonas and Other Gram-Negative BacilliRisk Factors for MRSA
      IV antibiotic use within previous 3 mo

      Sepsis accompanying VAP

      Adult respiratory distress syndrome before VAP

      Late-onset VAP (5 d or more in ICU/hospital)

      Dialysis just before VAP
      • Treatment in an ICU setting with the following:
        • 1.
          >10% of gram-negative isolates are resistant to one or more antibiotics indicated for VAP
        • 2.
          Local antimicrobial susceptibilities are unknown
      • Treatment in a medical ward/ICU in which:
        • 1.
          >10%–20% of Staphylococcus aureus isolates are MRSA
        • 2.
          Prevalence of MRSA is unknown
      Abbreviations: IV, intravenous; MDR, multidrug-resistant; MRSA, methicillin-resistant S. aureus; VAP, ventilator-associated pneumonia.
      For late-onset and/or MDR factor patients, appropriate antibiotic options would include one or more of the following
      • Amanullah S.
      • Mosenifar Z.
      Ventilator-associated pneumonia overview of nosocomial pneumonias.
      :
      • Antipseudomonal cephalosporins (eg, Cefepime, ceftazidime)
      • Antipseudomonal carbapenems (imipenem or meropenem)
      • Beta-lactam/beta-lactamase inhibitors (piperacillin-tazobactam) with an antipseudomonal fluoroquinolone (ciprofloxacin) or aminoglycoside plus linezolid or vancomycin (if MRSA risk factors are present)
      • Telavancin is indicated for VAP for susceptible isolates of S. aureus when other therapies are not suitable.
      Dose and frequency of administration of the antibiotic choices discussed earlier are documented extensively elsewhere.
      • File T.M.
      Treatment of hospital-acquired and ventilator-associated pneumonia in adults.
      Atypical antibiotic choices, such as colistin, polymyxin B, telavancin, inter alia, are rarely indicated but can be used when antimicrobial resistance warrants these agents.
      • Kalil A.C.
      • Metersky M.L.
      • Klompas M.
      • et al.
      Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.
      Typically, consultation with an infectious disease physician or clinical pharmacist with expertise and familiarity when using these drugs is a sine qua non.
      • Kalil A.C.
      • Metersky M.L.
      • Klompas M.
      • et al.
      Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.

      Pediatric Pneumonia

      Epidemiology

      Pneumonia is a very common affliction of childhood. Pneumonia accounts for 13% of infectious illnesses in infants and toddlers younger than 2 years.
      • Bennett N.J.
      • Domachowske J.
      • Steele R.
      Pediatric pneumonia.
      Worldwide, approximately 150 million new cases of pneumonia occur annually among children younger than 5 years.
      • Bennett N.J.
      • Domachowske J.
      • Steele R.
      Pediatric pneumonia.
      Pneumonia is the leading cause of death in children younger than 5 years in developing countries, accounting for 16% of all deaths of children younger than 5 years and killing 920,136 children in 2015.
      • Black R.E.
      • Cousens S.
      • Johnson H.L.
      • et al.
      Child Health Epidemiology Reference Group of WHO and UNICEF
      Global, regional, and national causes of child mortality in 2008: a systematic analysis.

      World Health Organization Pneumonia. Fact sheet No. 331. 2016. Available at: http://www.who.int/mediacentre/factsheets/fs331/en/index.html. Accessed February 20, 2018.

      Most childhood pneumonia (CP) can be treated in the outpatient setting. The rate of hospitalization for CP through age 18 years varies per year, but in 2006 it was 201.1 per 100 000.
      • Lee G.E.
      • Lorch S.A.
      • Sheffler-Collins S.
      • et al.
      National hospitalization trends for pediatric pneumonia and associated complications.
      Infants younger than 1 year had the highest rate of hospitalization (912.9 per 100 000), whereas children aged 13 to 18 years had the lowest rate (62.8 per 100 000).
      • Lee G.E.
      • Lorch S.A.
      • Sheffler-Collins S.
      • et al.
      National hospitalization trends for pediatric pneumonia and associated complications.

      Diagnosis

      Signs and symptoms of CP are often nonspecific and depend on several factors including age, microbial organism, and underlying health of the patient. Clinical acumen is key to successfully diagnosing CP. The universal symptom of CP is cough. Other symptoms may include chest pain, headache, arthralgia, nausea, and abdominal pain.
      • Stuckey-Schrock K.
      • Hayes B.L.
      • George C.M.
      Community-acquired pneumonia in children.
      Most common signs to look for include fever, tachypnea, labored breathing, rhonchi, crackles, and wheezing.
      • Stuckey-Schrock K.
      • Hayes B.L.
      • George C.M.
      Community-acquired pneumonia in children.
      Other physical signs to identify include grunting, nasal flaring, and chest retractions because these increase the likelihood of CP.
      • Margolis P.
      • Gadomski A.
      The rational clinical examination. Does this infant have pneumonia?.
      Diagnostic testing is usually performed, when available, and would include assessment of oxygen saturation by pulse oximetry, chest radiograph, complete blood cell count, respiratory microbial panel by PCR, ultrasound of the chest (when medically indicated), and cultures. Disagreement about whether blood cultures are warranted exists in the literature. As per a recent study, blood cultures have not been shown to assist with clinical management in children hospitalized with pneumonia.
      • Neuman M.I.
      • Hall M.
      • Lipsett S.C.
      • et al.
      Utility of blood culture among children hospitalized with community-acquired pneumonia.
      The Infectious Diseases Society of America, however, recommends blood cultures for all hospitalized children with pneumonia.
      • Bradley J.S.
      • Byington C.L.
      • Shah S.S.
      • 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.

      Etiology of pneumonia

      Etiologic microbial organisms differ, depending on age of the child. In infants, toddlers, and preschoolers, viruses predominate (Table 8). Less common bacterial organisms may infect newborns (see Table 8). In older children, bacteria are the more common culprit (Table 9). Atypical organisms may be involved when children are immunocompromised or have other underlying comorbidities (see Table 9).
      Table 8Etiology of childhood pneumonia (age 0–5 years)
      Data from Bennett NJ, Domachowske J, Steele R. Pediatric pneumonia. Medscape. 2017; and Stuckey-Schrock K, Hayes BL, George CM. Community-acquired pneumonia in children. Am Fam Physician 2012;86(7):661–7.
      VirusesBacteria
      RSVStreptococcus pneumoniae
      Parainfluenza types 1, 2, 3Hemophilus influenzae type B
      Influenza A and BStreptococcus pyogenes
      AdenovirusStaphylococcus aureus
      RhinovirusMycoplasma pneumoniae
      CoronavirusChlamydia pneumoniae/Chlamydia trachomatis
      hMPVBordetella pertussis
      HSVEscherichia coli
      VZVKlebsiella pneumoniae
      CMVListeria monocytogenes
      EnterovirusGroup B Streptococcus
      Abbreviations: CMV, cytomegalovirus; hMPV, human metapneumovirus; HSV, herpes simplex virus; RSV, respiratory syncytial virus; VZV, varicella zoster virus.
      Italicized/bolded are more common in newborns (age 0–30 days).
      Table 9Causes of childhood pneumonia (>5 years old)
      Data from Refs.
      • McDermott K.W.
      • Elixhauser A.
      • Sun R.
      Trends in hospital inpatient stays in the United States, 2005-2014. HCUP statistical brief #225.
      • Cisneros E.D.
      • Lazarte S.M.
      General infectious diseases.
      • Casey C.
      • Fullerton M.
      • Somerville N.
      Common questions about pneumonia in nursing home residents.
      BacteriaVirusesAtypical Organisms
      Mycoplasma pneumoniae

      Streptococcus pneumoniae

      Staphylococcus aureus

      Streptococcus pyogenes

      Chlamydia pneumoniae

      Hemophilus influenzae type B
      CMV

      Influenza A and B

      Rhinovirus

      Adenovirus

      RSV

      Parainfluenza

      hMPV

      Enterovirus
      Aspergillus

      Pneumocystis jirovecii

      Pseudomonas aeruginosa

      Burkholderia cepacia

      Histoplasma capsulatum

      Cryptococcus neoformans

      Blastomyces dermatitidis

      Mycobacterium tuberculosis

      Legionella pneumophila

      Oral anaerobes (aspiration)
      Abbreviations: CMV, cytomegalovirus; hMPV, human metapneumovirus; RSV, respiratory syncytial virus.

      Outpatient versus inpatient

      In order to provide optimal care to a child with pneumonia, it is important to determine the severity of the pneumonia and the child’s clinical status. Most children will not require inpatient admission; criteria exist to help stratify severity of pneumonia and necessity of hospitalization (Box 1 and 2).
      Criteria for childhood pneumonia hospitalization
      • Infants younger than 3 to 6 months with suspected bacterial CAP
      • Suspected or documented CAP caused by a pathogen with increased virulence, such as community-associated methicillin-resistant Staphylococcus aureus
      • Temperature greater or equal to 38.5 C (101.3 F)
      • Children and infants for whom there is concern about careful observation at home or who are unable to comply with therapy or unable to be followed-up
      • Children and infants who have respiratory distress and hypoxemia (oxygen saturation <92%) (see Table 2)
      • Children and infants with comorbidities (eg, asthma, cystic fibrosis, congenital heart disease, diabetes mellitus, neuromuscular disease)
      • Poor feeding and/or signs of dehydration
      Abbreviation: CAP, community-acquired pneumonia.
      Signs of respiratory distress
      • Tachypnea: RR
      • Age 0 to 2 months: greater than 60; age 2 to 12 months: greater than 50; age 1 to 5 years: greater than 40; age greater than 5 years: greater than 20
      • Dyspnea
      • Retractions: suprasternal, intercostal, or subcostal
      • Grunting
      • Nasal flaring
      • Apnea
      • Altered mental status
      • Pulse oximetry measurement less than 90% on room air
      Abbreviation: RR, respiratory rate.

      Antibiotics

      Choosing an antibiotic for CP is initially always an empirical process and based on local and regional microbial susceptibility and resistance patterns, along with the child’s age, immunization status, and any underlying, preexisting health conditions.
      • Bennett N.J.
      • Domachowske J.
      • Steele R.
      Pediatric pneumonia.
      • Stuckey-Schrock K.
      • Hayes B.L.
      • George C.M.
      Community-acquired pneumonia in children.

      Barson WJ. Pneumonia in children: inpatient treatment. 2018. Available at: http://www.uptodate.com/. Accessed January 16, 2018.

      Cincinnati Children’s Hospital Medical Center. Evidence-based care guideline. Community acquired pneumonia in children 60 days through 17years of age. Available at: file:///C:/Users/sgrief/Downloads/Community%20Acquired%20Pneumona%20Great%20001.pdf. Accessed February 20, 2018.

      Most children can be treated with oral antibiotics in the outpatient setting. First-line and preferred agent is still amoxicillin.
      • Bennett N.J.
      • Domachowske J.
      • Steele R.
      Pediatric pneumonia.
      • Stuckey-Schrock K.
      • Hayes B.L.
      • George C.M.
      Community-acquired pneumonia in children.
      • Bradley J.S.
      • Byington C.L.
      • Shah S.S.
      • 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.

      Cincinnati Children’s Hospital Medical Center. Evidence-based care guideline. Community acquired pneumonia in children 60 days through 17years of age. Available at: file:///C:/Users/sgrief/Downloads/Community%20Acquired%20Pneumona%20Great%20001.pdf. Accessed February 20, 2018.

      Alternative agents are cephalosporins and macrolide antibiotics; however, increasing resistance to penicillin derivatives and macrolides should be noted
      • Neuman M.I.
      • Kelley M.
      • Harper M.B.
      • et al.
      Factors associated with antimicrobial resistance and mortality in pneumococcal bacteremia.
      (Table 10). Quinolones can be considered in cases where there are no reasonable alternatives due to MDR pathogens or when an oral antibiotic is deemed optimal. Quinolones have been linked to development of childhood tendonitis/tendinopathy, yet recent literature indicates these disabling side effects are rare. Inpatient treatment guidelines have also been established (Table 11). Isolation of the particular microbial organism is ideal, but not required, in order to determine duration of therapy. Uncomplicated pneumonia treatment in the outpatient setting usually should last 5 to 10 days.
      • Stuckey-Schrock K.
      • Hayes B.L.
      • George C.M.
      Community-acquired pneumonia in children.
      Inpatient admission for pneumonia warrants longer duration of antibiotic therapy, typically 7 to 10 days of combined parenteral and oral therapy or at least 1 week after becoming afebrile.

      Barson WJ. Pneumonia in children: inpatient treatment. 2018. Available at: http://www.uptodate.com/. Accessed January 16, 2018.

      Complicated cases of pneumonia will require a minimum of 2 weeks of therapy once lack of fever is confirmed and may be extended for up to 4 weeks.

      Barson WJ. Pneumonia in children: inpatient treatment. 2018. Available at: http://www.uptodate.com/. Accessed January 16, 2018.

      The switch from parenteral to oral therapy may occur after 24 to 48 hours of documented lack of fever but is not always practical in complicated and/or ICU-admitted patients.
      • Dagan R.
      • Syrogiannopoulos G.
      • Ashkenazi S.
      • et al.
      Parenteral-oral switch in the management of pediatric pneumonia.
      Table 10Outpatient childhood pneumonia antibiotic treatment guidelines
      Adapted from Cincinnati Children’s Hospital Medical Center. Evidence-based care guideline. Community acquired pneumonia in children 60 days through 17 years of age. Available at: https://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/2011%20CAP%20in%20Children.pdf Accessed February 20, 2018; with permission.
      AgePreferred/First-LineAlternative/Second-Line
      0–5 y
       ViralNo treatmentAntiviral against influenza
       BacterialAmoxicillinAmoxicillin-clavulanate/third-generation cephalosporin
       Atypical bacterialMacrolideConsult infectious disease
       Allergy to any of the aboveThird-generation cephalosporin/clindamycinQuinolone
      5–16 y
       ViralNo treatmentAntiviral against influenza
       BacterialAmoxicillinAmoxicillin-clavulanate/third-generation cephalosporin
       Atypical bacterialMacrolide or doxycyclineQuinolone if older than 8 years and suspect MDR organism
       Allergy to any of the aboveThird-generation cephalosporin/clindamycinQuinolone
      Table 11Inpatient childhood pneumonia antibiotic treatment guidelines
      Adapted from Cincinnati Children’s Hospital Medical Center. Evidence-based care guideline. Community acquired pneumonia in children 60 days through 17 years of age. Available at: file:///C:/Users/sgrief/Downloads/Community%20Acquired%20Pneumona%20Great%20001.pdf. Accessed February 20, 2018; with permission.
      Age/CategoryPreferred/First-LineAlternative/Second-Line
      0–6 mo
       BacterialIV penicillin derivative and third-generation cephalosporinAminoglycoside with PCN derivative; macrolide if suspect atypical organism
      6 mo–5 y
       BacterialIV penicillin derivative (PCN or ampicillin)Third-generation cephalosporin
       MRSAVancomycin or clindamycin (in addition to beta-lactam antibiotic)Vancomycin or clindamycin (in addition to beta-lactam antibiotic)
       Atypical bacterial infectionMacrolideMacrolide (in addition to beta-lactam antibiotic)
       Allergy to any of the aboveThird-generation cephalosporin/clindamycinQuinolone
      5–16 y
       BacterialIV penicillin derivative (PCN or ampicillin)Third-generation cephalosporin
       MRSAVancomycin or clindamycin (in addition to beta-lactam antibiotic)Vancomycin or clindamycin (in addition to beta-lactam antibiotic); linezolid in children aged 12 y or older
       Atypical bacterial infectionMacrolideMacrolide (in addition to beta-lactam antibiotic)
       Allergy to any of the aboveThird-generation cephalosporin/clindamycinQuinolone
       Severe pneumonia/ICU admissionThird-generation cephalosporin and macrolide/vancomycin + third-gen ceph + macrolideThird-generation cephalosporin and doxycycline/vancomycin + third-gen ceph + macrolide + (optional) Nafcillin + antiviral
      Abbreviations: Ceph, cephalosporin; IV, intravenous; PCN, penicillin.

      Summary

      Pneumonia is a common, well-recognized respiratory infection seen in primary care settings. Triage of the usual presenting symptoms will generally set into motion a typical course of action, including physical examination and possibly imaging to confirm clinical suspicion. Further testing depends on treatment venue (outpatient vs inpatient) and other specific criteria (see Table 3). Empirical antibiotic therapy is the cornerstone of treatment, and knowledge of local and regional microbial susceptibility and resistance will bolster the success rate of outpatient management of pneumonia, regardless of demographic and/or accompanying morbidities. Special circumstances and scenarios that may occur, including nonresolving pneumonias, pediatric or geriatric populations, travel-related infections, among others, will necessitate a more careful attention to history, physical examination, and antibiotic selection.

      References

        • McDermott K.W.
        • Elixhauser A.
        • Sun R.
        Trends in hospital inpatient stays in the United States, 2005-2014. HCUP statistical brief #225.
        Agency for Healthcare Research and Quality, Rockville (MD)2017 (Available at:)
      1. Rui P, Kang K. National Hospital Ambulatory Medical Care Survey: 2014 emergency department summary tables. Available at: http://www.cdc.gov/nchs/data/ahcd/nhamcs_emergency/2014_ed_web_tables.pdf. Accessed January 16, 2018.

        • Torio C.
        • Moore B.
        National inpatient hospital costs: the most expensive conditions by payer, 2013. HCUP statistical brief #204.
        Agency for Healthcare Research and Quality, Rockville (MD)2016 (Available at:)
        • Jain S.
        • Self W.H.
        • Wunderink R.G.
        • et al.
        Community-acquired pneumonia requiring hospitalization among U.S. adults.
        N Engl J Med. 2015; 373: 415-427
        • Cisneros E.D.
        • Lazarte S.M.
        General infectious diseases.
        in: De Fer T. Sateia H. The Washington manual of outpatient internal medicine. Lippincott Williams & Wilkins, Philadelphia2015: 523-526
        • Kaysin A.
        • Viera A.J.
        Community- acquired pneumonia in adults: diagnosis and management.
        Am Fam Physician. 2016; 94: 698-706
        • Diehr P.
        • Wood R.W.
        • Bushyhead J.
        • et al.
        Prediction of pneumonia in outpatients with acute cough: a statistical approach.
        J Chronic Dis. 1984; 37: 215-225
        • Simel D.L.
        • Metlay J.P.
        Pneumonia, adult, community-acquired.
        in: Simel D.L. Rennie D. The rational clinical examination: evidence-based clinical diagnosis. McGraw-Hill, New York2009 (Available at:) (Accessed December 17, 2017)
        • Casey C.
        • Fullerton M.
        • Somerville N.
        Common questions about pneumonia in nursing home residents.
        Am Fam Physician. 2015; 92: 612-620
        • Ebell M.H.
        Predicting pneumonia in adults with respiratory illness.
        Am Fam Physician. 2007; 76: 560-562
        • Mandell L.
        • Wunderink R.
        • Anzueto A.
        • et al.
        Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
        Clin Infect Dis. 2007; 44: S27-S72
        • Lim W.
        • Baudouin S.
        • George R.
        • et al.
        BTS guidelines for the management of community acquired pneumonia in adults: update 2009.
        Thorax. 2009; 64: iii1-iii55
        • Gupta D.
        • Agarwal R.
        • Aggarwal A.N.
        • et al.
        Guidelines for diagnosis and management of community- and hospital-acquired pneumonia in adults: joint ICS/NCCP(I) recommendations.
        Lung India. 2012; 29: S27-S62
      2. Tuberculosis (TB) | CDC. Cdcgov. 2018. Available at: https://www.cdc.gov/tb/default.htm. Accessed February 24, 2018.

        • Chalmers J.
        • Singanayagam A.
        • Akram A.
        • et al.
        Severity assessment tools for predicting mortality in hospitalised patients with community-acquired pneumonia. Systematic review and meta-analysis.
        Thorax. 2010; 65: 878-883
        • Lim W.S.
        • van der Eerden M.M.
        • Laing R.
        • et al.
        Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study.
        Thorax. 2003; 58: 377-382
        • Pakhale S.
        • Mulpuru S.
        • Verheij T.J.M.
        • et al.
        Antibiotics for community-acquired pneumonia in adult outpatients.
        Cochrane Database Syst Rev. 2014; 2014 (CD002109)
        • Uranga A.
        • España P.
        • Bilbao A.
        • et al.
        Duration of antibiotic treatment in community-acquired pneumonia.
        JAMA Intern Med. 2016; 176: 1257
        • Chen Y.
        • Li K.
        • Pu H.
        • et al.
        Corticosteroids for pneumonia.
        Cochrane Database Syst Rev. 2011; (CD007720)
        • Siemieniuk R.
        • Alonso-Coello P.
        • Guyatt G.
        Corticosteroid therapy for patients hospitalized with community-acquired pneumonia.
        Ann Intern Med. 2016; 164: 636
        • Feldman C.
        • Anderson R.
        Corticosteroids in the adjunctive therapy of community-acquired pneumonia: an appraisal of recent meta-analyses of clinical trials.
        J Thorac Dis. 2016; 8: E162-E171
        • Sager R.
        • Kutz A.
        • Mueller B.
        • et al.
        Procalcitonin-guided diagnosis and antibiotic stewardship revisited.
        BMC Med. 2017; 15: 15
        • Schuetz P.
        • Wirz Y.
        • Sager R.
        • et al.
        Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections.
        Cochrane Database Syst Rev. 2017; (CD007498)
        • Tan L.
        • Louie S.
        Unresolved Acute Pneumonia: a “BAD OMEN”.
        Consultant. 2017; : 500-503
      3. Cdc.gov. Pneumococcal vaccination | what you should know | CDC. [online]. 2017. Available at: https://www.cdc.gov/vaccines/vpd/pneumo/public/index.html. Accessed December 14, 2017.

        • Bonten M.
        • Huijts S.M.
        • Bolkenbaas M.
        • et al.
        Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.
        N Engl J Med. 2015; 372: 1114-1125
        • Centers for Disease Control and Prevention
        Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23).
        MMWR Morb Mortal Wkly Rep. 2010; 59: 1102-1105
        • Moberley S.
        • Holden J.
        • Tatham D.P.
        • et al.
        Vaccines for preventing pneumococcal infection in adults.
        Cochrane Database Syst Rev. 2013; (CD000422)
        • Sialer S.
        • Liapikou A.
        • Torres A.
        What is the best approach to the nonresponding patient with community-acquired pneumonia?.
        Infect Dis Clin North Am. 2013; 27: 189-203
        • Trimble A.
        • Moffat V.
        • Collins A.
        Pulmonary infections in the returned traveler.
        Pneumonia (Nathan). 2017; 9: 1
        • Black A.
        Non-infectious mimics of community-acquired pneumonia.
        Pneumonia. 2016; 8: 2
        • Faverio P.
        • Aliberti S.
        • Bellelli G.
        • et al.
        The management of community-acquired pneumonia in the elderly.
        Eur J Intern Med. 2014; 25: 312-319
        • Centers for Disease Control and Prevention
        CDC yellow book 2018: health information for international travel.
        Oxford University Press, New York2017
        • Meltzer E.
        • Schwartz E.
        Travel-related respiratory infections.
        in: Schwartz E. Tropical diseases in travelers. Wiley-Blackwell, Hoboken (NJ)2009: 413-426
      4. Fairley JK. General approach to the returned traveler. In: Chapter 5: post-travel evaluation. Centers for disease control and prevention. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2018/post-travel-evaluation/general-approach-to-the-returned-traveler. Accessed February 26, 2018.

        • Segel M.J.
        • Schwartz E.
        Histoplasmosis and other endemic fungal infections.
        in: Schwartz E. Tropical diseases in travelers. Wiley-Blackwell, Hoboken (NJ)2009: 282-293
        • Amanullah S.
        • Mosenifar Z.
        Ventilator-associated pneumonia overview of nosocomial pneumonias.
        Medscape. 2015;
        • File T.M.
        Treatment of hospital-acquired and ventilator-associated pneumonia in adults.
        UpToDate. 2018;
        • Cook D.J.
        • Walter S.D.
        • Cook R.J.
        • et al.
        Incidence of and risk factors for ventilator-associated pneumonia in critically ill patients.
        Ann Intern Med. 1998; 129: 433-440
        • Fabregas N.
        • Ewig S.
        • Torres A.
        • et al.
        Clinical diagnosis of ventilator-associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies.
        Thorax. 1999; 54: 867-873
        • Horan T.
        • Gaynes R.
        Survillence of nosocomial infection.
        in: Mayhall C. Hospital epidemiology and infection control. 3rd edition. Lippincott Williams and Wilkins, Philadelphia2004: 1659-1702
        • El Kuti
        • Patel A.A.
        • Coleman C.I.
        Impact of inappropriate antibiotic therapy on mortality in patients with ventilator-associate pneumonia and blood stream infection: a meta-analysis.
        J Crit Care. 2008; 23: 91
        • Muscedere J.G.
        • Shorr A.F.
        • Jiang X.
        • et al.
        The adequacy of timely empiric antibiotic therapy for ventilator-associate pneumonia: an important determinant of outcome.
        J Crit Care. 2012; 27: 322.e7
        • Paul M.
        • Shani V.
        • Muchtar E.
        • et al.
        Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis.
        Antimicrob Agents Chemother. 2010; 54: 4851
        • Swanson J.M.
        • Wells D.L.
        Empirical antibiotic therapy for ventilator-associated pneumonia.
        Antibiotics (Basel). 2013; 2: 339
        • Thakuria B.
        • Singh P.
        • Agrawal S.
        • et al.
        Profile of infective microorganisms causing ventilator-associated pneumonia: A clinical study from resource limited intensive care unit.
        J Anaesthesiol Clin Pharmacol. 2013; 29: 361-366
        • Rello J.
        • Torres A.
        Microbial causes of ventilator-associated pneumonia.
        Semin Respir Infect. 1996; 11: 24-31
        • Kalil A.C.
        • Metersky M.L.
        • Klompas M.
        • et al.
        Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society.
        Clin Infect Dis. 2016; 63: e61
        • Beardsley J.R.
        • Williamson J.C.
        • Johnson J.W.
        • et al.
        Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia.
        Chest. 2006; 130: 787
        • Bennett N.J.
        • Domachowske J.
        • Steele R.
        Pediatric pneumonia.
        Medscape. 2017;
        • Black R.E.
        • Cousens S.
        • Johnson H.L.
        • et al.
        • Child Health Epidemiology Reference Group of WHO and UNICEF
        Global, regional, and national causes of child mortality in 2008: a systematic analysis.
        Lancet. 2010; 375: 1969-1987
      5. World Health Organization Pneumonia. Fact sheet No. 331. 2016. Available at: http://www.who.int/mediacentre/factsheets/fs331/en/index.html. Accessed February 20, 2018.

        • Lee G.E.
        • Lorch S.A.
        • Sheffler-Collins S.
        • et al.
        National hospitalization trends for pediatric pneumonia and associated complications.
        Pediatrics. 2010; 126: 204-213
        • Stuckey-Schrock K.
        • Hayes B.L.
        • George C.M.
        Community-acquired pneumonia in children.
        Am Fam Physician. 2012; 86: 661-667
        • Margolis P.
        • Gadomski A.
        The rational clinical examination. Does this infant have pneumonia?.
        JAMA. 1998; 279: 308-313
        • Neuman M.I.
        • Hall M.
        • Lipsett S.C.
        • et al.
        Utility of blood culture among children hospitalized with community-acquired pneumonia.
        Pediatrics. 2017; 140 ([pii:e20171013])
        • Bradley J.S.
        • Byington C.L.
        • Shah S.S.
        • 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
      6. Barson WJ. Pneumonia in children: inpatient treatment. 2018. Available at: http://www.uptodate.com/. Accessed January 16, 2018.

      7. Cincinnati Children’s Hospital Medical Center. Evidence-based care guideline. Community acquired pneumonia in children 60 days through 17years of age. Available at: file:///C:/Users/sgrief/Downloads/Community%20Acquired%20Pneumona%20Great%20001.pdf. Accessed February 20, 2018.

        • Neuman M.I.
        • Kelley M.
        • Harper M.B.
        • et al.
        Factors associated with antimicrobial resistance and mortality in pneumococcal bacteremia.
        J Emerg Med. 2007; 32: 349-357
      8. Available at: http://www.aappublications.org/news/aapnewsmag/2016/10/31/Fluoroquinolones103116.full.pdf. Accessed February 20, 2018.

      9. Available at: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-fluoroquinolones-assessing-potential-risk-persistent-disabling-effects.html. Accessed February 20, 2018.

        • Dagan R.
        • Syrogiannopoulos G.
        • Ashkenazi S.
        • et al.
        Parenteral-oral switch in the management of pediatric pneumonia.
        Drugs. 1994; 47: 43