Community-acquired Pneumonia and Hospital- acquired Pneumonia a, b a Charles W. Lanks, MD *, Ali I. Musani, MD , David W. Hsia, MD KEYWORDS Community-acquired pneumonia Hospital-acquired pneumonia Pneumonia CAP HAP KEY POINTS Pneumonia is a common disease that requires a deep understanding of pathophysiology, epidemiology, and pharmacology to properly manage. Diagnostic strategies for pneumonia range from simple to highly complex depending on disease severity and likelihood of altering the empiric antibiotic regimen. Pneumonia management plans are tailored to each individual patient encounter and incor- porate knowledge of health care setting, pathogen type, and risk factors for antibiotic resistance. Complications from pneumonia are common and should prompt consultation with a pul- monary specialist when necessary. INTRODUCTION Pneumonia is consistently among the leading causes of morbidity and mortality world- wide.1 Defined as acute infection of the lung parenchyma, it is caused by a wide va- riety of microorganisms, including bacteria, viruses, and fungi.2 Common categories of pneumonia include: Community-acquired pneumonia (CAP): infection acquired outside of the hospi- tal setting. Hospital-acquired pneumonia (HAP): infection acquired after at least 48 hours of hospitalization.3 Disclosure: The authors have no financial conflicts of interest. a Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, 1000 West Carson Street, Box 402, Torrance, CA 90509, USA; b Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Hospital, 12631 East 17th Street, Office #8102, Aurora, CO 80045, USA * Corresponding author. E-mail address: [email protected] Med Clin N Am - (2019) -–- https://doi.org/10.1016/j.mcna.2018.12.008 medical.theclinics.com 0025-7125/19/ª 2019 Elsevier Inc. All rights reserved. 2 Lanks et al Ventilator-associated pneumonia (VAP): subcategory of HAP that occurs in pa- tients receiving mechanical ventilation. Because of major differences in patho- physiology, microbiology, and therapy in VAP compared with non-VAP HAP, it is outside the scope of this review. Health care–associated pneumonia (HCAP): infection acquired in lower-acuity health care settings such as nursing homes and dialysis centers.3 It is now recog- nized that patients acquiring pneumonia in lower-acuity health care settings are not at increased risk for multidrug-resistant (MDR) pathogens4; therefore, HCAP was not included in the most recent treatment guidelines for CAP or HAP.2,5 PATHOPHYSIOLOGY Pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and gram- negative bacilli typically enter the lower respiratory tract through aspiration of oropha- ryngeal secretions. Microaspiration can occur on a regular basis, even in healthy individuals and particularly during sleep, but progression to pneumonia is rare. Pro- gression largely depends on the inoculum of pathogenic bacteria, volume of aspirate, frequency of aspiration, and virulence of aspirated bacteria relative to the host immune system.6 Colonization of the oropharynx with virulent organisms is affected by comor- bidities such as chronic malnutrition, alcoholism, and diabetes. These comorbidities lead to defects in the host immune response, such as deficiencies in local immuno- globulins, complement, and salivary fibronectins, which prevent bacterial surface binding. Intracellular bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp) and viruses tend to enter the lower respiratory tract via the inhalational route. Pro- gression to infection again depends on the inoculum of pathogenic organisms. How- ever, the microparticles in which that inoculum is suspended must also be small enough (typically <5 mm) to facilitate transit into the lower airways while continuing to evade local host defenses. EPIDEMIOLOGY Pneumonia remains a leading cause of hospitalization and death worldwide. In 2015, pneumonia was the eighth leading cause of death in the United States,1 the fourth leading cause of death worldwide, and leading cause of death in low-income coun- tries.7 However, the true incidence of CAP is likely underestimated. Patients with mild infections are less likely to seek medical attention and diagnosis may therefore go unrecognized. Microbiology Among patients who seek medical attention, S pneumoniae is by far the most commonly isolated bacterial pathogen, accounting for more than 25% of cases of CAP worldwide.8 The likelihood of disease being caused by a specific organism varies with disease severity (Table 1). Milder presentations are more likely to be caused by M pneumonia, C pneumoniae, and viruses, although S pneumoniae still predominates.9 More severe presentations commonly involve Staphylococcus aureus, Legionella, and H influenzae (see Table 1). This rough association between causative organism and disease severity lays the groundwork for empiric antimicro- bial therapy.2 The spectrum of causative organisms in HAP also includes gram-positive cocci such as S aureus and S pneumoniae10 but is more likely to involve gram-negative bacilli such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus coli, Community- and Hospital-acquired Pneumonia 3 Table 1 Causative organisms and suggested diagnostics by pneumonia type and severity Common Causative Organisms Suggested Diagnostics CAP: outpatient M pneumoniae, S pneumoniae, None routinely Chlamydophila pneumoniae, respiratory virusesa CAP: non-ICU, S pneumoniae, M pneumoniae, C Sputum bacterial culture low severity pneumoniae, respiratory virusesa Respiratory viral PCR CAP: non-ICU, S pneumoniae, Staphylococcus aureus, Sputum bacterial culture moderate H influenzae, Legionella species, Blood bacterial culture severity respiratory virusesa Respiratory viral PCR Pneumococcal urinary Ag Legionella urinary Ag CAP: ICU, high S pneumoniae, enteric gram-negative Sputum bacterial culture severity bacilli,b S aureus, H influenzae, Legionella Blood bacterial culture species, respiratory virusesa, Pseudomonas Respiratory viral PCR aeruginosa Pneumococcal urinary Ag Legionella urinary Ag Consider bronchoscopy HAP (non-VAP) S pneumoniae, enteric gram-negative bacilli, Sputum bacterial culture S aureus, P aeruginosa Blood bacterial culture Respiratory viral PCR Pneumococcal urinary Ag Abbreviations: Ag, antigen; ICU, intensive care unit; PCR, polymerase chain reaction. a Such as influenza, parainfluenza, and respiratory syncytial virus. b Such as Klebsiella pneumoniae, Enterococcus coli, and Enterobacter spp. and Enterobacter spp.11 The presence of multidrug resistance is affected by a combi- nation of patient-specific and hospital-specific risk factors such as recent antibiotic use, length of current hospitalization, presence of structural lung disease, and local hospital resistance patterns. Commonly encountered MDR pathogens include methicillin-resistant S aureus (MRSA), Pseudomonas, and extended-spectrum b-lac- tamase (ESBL)–producing gram-negative enteric bacteria.12,13 Viruses, including influenza, are common causative organisms depending on sea- sonal variations.14 In addition, viruses have been found to play an increasingly recog- nized role in HAP.15 However, it should be noted that the mere detection of a viral pathogen does not guarantee causality because there is a strong association between viral infection and secondary bacterial coinfection.16 Less commonly encountered organisms include Mycobacterium tuberculosis, non- tuberculous mycobacteria, Chlamydophila spp, Coxiella, and fungi such as Cocci- dioides, Blastomyces, Histoplasma, Cryptococcus, and Aspergillus. Suspicion for these should depend on individual patient risk factors, including immunosuppression and travel history. Risk Factors and Genetics The risk of acquiring pneumonia increases with patient age and the presence of comorbidities.17 These comorbidities include chronic respiratory diseases, such as chronic obstructive pulmonary disease and bronchiectasis, as well as nonrespiratory problems such as cardiovascular and renal diseases. Comorbidities such as epilepsy, dementia, and stroke increase pneumonia risk as well, possibly via increased risk of aspiration. Lifestyle-related factors such as tobacco use, alcohol use, chronic 4 Lanks et al malnutrition, and poor dental hygiene also confer increased risk.18 The presence of structural lung disease, recent antibiotic use, and corticosteroid use are risk factors for gram-negative infection.19 More recently, several genetic risk factors for CAP have also been identified.20 Var- iants in the proto-oncogene tyrosine-protein kinase FER gene, which regulates cell adhesion, migration, and chemotaxis, have been associated with reduced risk of death from pneumonia.21 CLINICAL PRESENTATION The classic or typical presentation of pneumonia is characterized by the acute onset of infectious lower respiratory tract symptoms in conjunction with consistent radio- graphic findings. Fever, cough, pleurisy, dyspnea, and increased sputum production are common symptoms of pneumonia. In many patients, the presentation of pneu- monia can be atypical and characterized predominantly by nonrespiratory symptoms such as malaise, myalgia, confusion, and diarrhea. In elderly individuals, this type of presentation may occur with increased frequency,22,23 leading to delays in therapy and increased mortality.24 The grouping of clinical presentations into typical and atypical categories was pre- viously thought to be useful in