INTRODUCTION — Aspiration pneumonia refers to adverse pulmonary consequences due to entry of gastric or oropharyngeal fluids, which may contain bacteria and/or be of low pH, or exogenous substances (eg, ingested food particles or liquids, mineral oil, salt or fresh water) into the lower airways .
The predisposing conditions, clinical syndromes, diagnosis, and treatment of aspiration pneumonia will be reviewed here. Community-acquired pneumonia, hospital-acquired pneumonia, empyema, and lung abscess are discussed separately. (See "Overview of community-acquired pneumonia in adults" and "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia" and "Treatment of hospital-acquired and ventilator-associated pneumonia in adults" and "Lung abscess in adults".)
DEFINITIONS — The term aspiration pneumonia should be reserved specifically for pneumonitis resulting from aspiration of oropharyngeal or gastric contents (table 1). This is typically due to impairment of the clearance defenses (eg, depressed sensorium, glottic closure, or cough reflex). The character of the inoculum, underlying pulmonary conditions, and presentation assist in distinguishing the three most common clinical syndromes within the category of aspiration pneumonia, namely chemical pneumonitis, bacterial infection, and airway obstruction . Although there may occasionally be overlap and it is often difficult to classify individual cases with certainty, this classification scheme is essential to an understanding of aspiration pneumonia.
●Chemical pneumonitis refers to the aspiration of substances (eg, acidic gastric fluid) that cause an inflammatory reaction in the lower airways, independent of bacterial infection.
●Bacterial aspiration pneumonia refers to an active infection caused by inoculation of large amounts of bacteria into the lungs via orogastric contents. These bacteria may be aerobic, anaerobic or a mixture. Risk factors for aspiration pneumonia include neurologic disorders, reduced consciousness, esophageal disorders, vomiting, and witnessed aspiration .
In contrast, pathogens that commonly produce bacterial pneumonia, such as Streptococcus pneumoniae, Haemophilus influenzae, gram-negative bacilli, and Staphylococcus aureus, are relatively more virulent bacteria so that smaller inocula and more subtle aspirations may be sufficient to trigger clinically overt pneumonia.
●Mechanical obstruction – Aspiration of fluid or particulate matter that obstructs the airway or triggers reflex airway closure but without an associated parenchymal inflammatory reaction.
An alternative classification is "aspiration pneumonitis" in reference to lung injury due to gastric acid and "aspiration pneumonia" in reference to pneumonia due to bacterial infection .
PREDISPOSING CONDITIONS — Aspiration of small amounts of oropharyngeal secretions is common even in healthy individuals and usually resolves without detectable sequelae . Sensitive tests show that at least one-half of healthy adults aspirate during sleep [6,7]. Thus, most episodes of aspiration are subclinical and/or rapidly resolve without clinical manifestations. The small fraction of aspiration events that do proceed to clinically manifest disease appear to depend upon the volume and contents of the inoculum as well as failures of host defense mechanisms.
Conditions that predispose to aspiration include processes that reduce consciousness, interfere with normal swallowing, impair airway clearance (ciliary function or cough), or lead to frequent or large-volume aspiration (table 2) [1,8]. Conditions that lead to frequent or large-volume aspiration also increase the probability of aspiration pneumonitis (table 2). Examples include the following:
●Reduced consciousness (eg, due to sedative or antipsychotic medications, alcohol or drug use, anesthesia, generalized seizures) can compromise the cough reflex and glottic closure [1,8,9]
●Dysphagia from neurologic deficits (see "Swallowing disorders and aspiration in palliative care: Definition, consequences, pathophysiology, and etiology")
●Disorders of the upper gastrointestinal tract including esophageal disease, surgery involving the upper airways or esophagus, and gastric reflux (see "Approach to the evaluation of dysphagia in adults")
●Mechanical disruption of the glottic closure or lower esophageal sphincter due to tracheostomy, endotracheal intubation, head and neck cancer, bronchoscopy, upper endoscopy, and nasogastric feeding
●Pharyngeal anesthesia and miscellaneous conditions such as protracted vomiting, large-volume tube feedings, feeding gastrostomy, the recumbent position, and near-drowning
●Poor dental hygiene is also associated with increased risk of aspiration pneumonia, presumably because aspiration in this setting is associated with higher inoculums of oral flora and potentially a shift to more pathogenic bacteria [4,10-16]
●Increasing age is an important risk factor for aspiration pneumonia, largely due to diseases related to aging (eg, stroke, degenerative neurologic disease, altered mental status due to medications), with patients in long-term care facilities and those with comorbidities being particularly vulnerable [17-19]
●Cardiac arrest has been associated with a particularly high incidence of pneumonia, presumably due to loss of consciousness as well as aspiration of oropharyngeal and gastric contents in the context of cardiopulmonary resuscitation, bag-valve mask ventilation, and emergent intubation [20,21]
There is an association between use of acid-suppressive medications and community-acquired pneumonia, ventilator-associated pneumonia, and hospital-acquired pneumonia. The assumed common mechanism in all of these conditions is loss of the gastric acid barrier resulting in a higher bacterial load in gastric contents and thus in the lungs when aspiration of gastric contents occurs (a phenomenon that is both common and subtle). (See "Epidemiology, pathogenesis, and microbiology of community-acquired pneumonia in adults", section on 'Predisposing host conditions' and "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Role of gastric pH' and "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Pneumonia'.)
In a prospective population-based study of 1946 patients with pneumonia admitted to the hospital from continuing care facilities (CCFs) or the community , the most common risk factor for community-acquired aspiration pneumonia was impaired consciousness due to alcohol, drugs, or hepatic failure, whereas the most common risk factor for CCF-acquired aspiration pneumonia was neurologic disease that resulted in dysphagia (present in 72 percent of CCF-acquired aspiration pneumonias). In another report that included 134 older adult patients (mean age 84 years) hospitalized with pneumonia, 55 percent had oropharyngeal dysphagia based on a water swallow test .
CHEMICAL PNEUMONITIS — The prototype and best studied clinical example of chemical pneumonitis is that associated with the aspiration of gastric acid first described by Mendelson in 1946 and sometimes referred to as Mendelson syndrome [24,25]. Chemical aspiration pneumonitis also occurs perioperatively, most often during intubation or extubation for anesthesia or during procedures like laryngoscopy. Pneumonitis due to hydrocarbon inhalation is described separately. (See "Overview of the management of postoperative pulmonary complications", section on 'Chemical pneumonitis' and "Acute hydrocarbon exposure: Clinical toxicity, evaluation, and diagnosis".)
Mendelson’s original series included 61 obstetrical patients who aspirated gastric contents during ether anesthesia . Respiratory distress and cyanosis rapidly followed, usually within two hours of a witnessed aspiration . Chest radiographs showed opacities that were usually located in one or both lower lobes. Despite the initial severity of the illness, all 61 patients had a rapid clinical recovery within 24 to 36 hours, with radiographic resolution within four to seven days without the use of antimicrobial therapy.
Subsequent studies have shown that this form of aspiration pneumonia sometimes follows a fulminant course that may result in acute respiratory distress syndrome (ARDS) . In patients with aspiration pneumonia resulting in ARDS, blood gas studies usually show that the partial pressure of oxygen (PaO2) is reduced, accompanied by a normal or low partial pressure of carbon dioxide (PaCO2) with respiratory alkalosis. Factors that contribute to hypoxemia include noncardiogenic pulmonary edema, reduced surfactant activity, reflex airway closure, alveolar hemorrhage, and hyaline membrane formation. Pulmonary function tests show decreased compliance, abnormal ventilation-perfusion, and reduced diffusing capacity. (See "Acute respiratory distress syndrome: Clinical features, diagnosis, and complications in adults".)
The difference in the clinical course of chemical pneumonitis since the initial report by Mendelson compared with more recent studies may be explained by the differences in the type of patients who develop this complication. Mendelson described healthy, young obstetrical patients, whereas the subjects of subsequent reports were often older, debilitated, or burdened with comorbid conditions [24,26]. Reporting bias may have also favored publication of more seriously ill patients, as a contrast to Mendelson’s original report.
Pathophysiology — The pathophysiology of acid pneumonitis has been studied extensively in experimental animals using intratracheal installation of acid [27-29]. These animal models demonstrated that an inoculum with a pH of ≤2.5 and relatively large volume (usually 1 to 4 mL/kg) was needed to cause chemical pneumonitis. This would translate to an inoculum of at least 70 mL of gastric acid in adult humans. It is probable that smaller volumes produce a more subtle process that either escapes clinical detection or causes a less fulminant form of pneumonitis. The clinical observation that patients with esophageal or gastric reflux experience frequent bouts of recurrent pneumonitis, often accompanied by pulmonary fibrosis, supports this concept [30,31].
The pathologic changes in the preceding animal models of acid pneumonitis evolve rapidly. Within three minutes, there is atelectasis, peribronchial hemorrhage, pulmonary edema, and degeneration of bronchial epithelial cells. By four hours, the alveolar spaces are filled with polymorphonuclear leukocytes and fibrin. Hyaline membranes are seen within 48 hours. The lung at this time is also grossly edematous and hemorrhagic with alveolar consolidation.
All of the findings described above have also been noted on autopsy of patients with fatal aspiration pneumonia. The presumed mechanism is the release of proinflammatory cytokines, especially tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 [32-34].
Bile may also elicit an inflammatory response in the lungs and has been found frequently in endotracheal tubes of patients on ventilators .
Clinical features — The following clinical features should raise the possibility of chemical pneumonitis [1,36,37]:
●Abrupt onset of symptoms, such as dyspnea, cough, hypoxemia, and tachycardia in a patient with risk factors for aspiration.
●Fever, which is usually low grade.
●Diffuse crackles or wheezes on lung auscultation.
●Opacities on chest imaging involving dependent pulmonary segments (image 1 and image 2). The dependent lobes in the upright position are the lower lobes. However, aspiration that occurs while patients are in the recumbent position may result in infection in the superior segments of the lower lobes and the posterior segments of the upper lobes. A minority of patients develop a radiographic pattern of acute respiratory distress syndrome with diffuse opacities.
Diagnosis — The diagnosis of chemical pneumonitis is usually presumptive based upon the clinical features and course noted above. After a suspected aspiration, chest radiograph abnormalities typically appear within two hours. Bronchoscopy, although usually not necessary, demonstrates erythema of the bronchi, indicating acid injury.
Treatment — Patients with an observed aspiration should have immediate oropharyngeal suctioning with the head turned to the side to prevent further aspiration, and those with an endotracheal tube in place should have immediate tracheal suctioning to clear fluids and particulate matter that may cause obstruction. The chemical injury that occurs with a gastric acid aspiration event occurs instantly in a manner that has been compared with a "flash burn," which is followed by rapid release of inflammatory mediators and neutrophil recruitment . Bronchoalveolar lavage, which may be used to clear particulate matter, will not protect the lungs from the chemical injury that is already in progress.
●Supportive care – The major therapeutic approach is to support oxygenation and provide mechanical ventilation for patients with respiratory failure. Supportive care for patients with acute respiratory distress syndrome (ARDS) is discussed separately. (See "Ventilator management strategies for adults with acute respiratory distress syndrome" and "Acute respiratory distress syndrome: Supportive care and oxygenation in adults".)
●Systemic glucocorticoids – The routine use of glucocorticoids in the treatment of chemical aspiration pneumonitis is discouraged, as observational studies in humans have not demonstrated clear benefit [1,39]. The administration of glucocorticoids for ARDS is discussed separately. (See "Acute respiratory distress syndrome: Supportive care and oxygenation in adults", section on 'Glucocorticoids'.)
●Empiric antibiotics – Clinical studies suggest that 13 to 26 percent of patients with observed aspiration events acquire pulmonary superinfections during the course of recovery [25,40,41]. Because it is difficult to exclude bacterial infection as a contributing factor in patients with aspiration, antibiotics are frequently prescribed at the time of the aspiration event . However, the high rate of spontaneous recovery from aspiration pneumonitis and observational comparisons of treated and untreated patients suggest that antibiotics may not be necessary for most patients . In a retrospective review of 200 patients with aspiration pneumonitis, for example, outcomes were similar for patients regardless of whether they received empiric antibiotics or not (no difference in need for intensive care or mortality) .
Thus, we reserve use of empiric antibiotics following an aspiration event for patients who have persistent or progressive respiratory impairment with systemic signs of inflammation (see 'Choice of regimen' below). In the subset of patients in whom we do opt to start antibiotics, we re-evaluate the need for continued antibiotic use after 24, 48, and 72 hours. If pulmonary function and systemic signs have returned to baseline, we typically stop antibiotics.
BACTERIAL PNEUMONIA — Bacterial aspiration pneumonia is caused by bacteria that normally reside in the upper airways or stomach. Historically, aspiration pneumonia has usually referred to an infection caused by less virulent bacteria, primarily oral anaerobes and streptococci, which are common constituents of the normal oral flora in patients prone to aspiration . More recent studies have disputed the dominance of anaerobic bacteria in aspiration pneumonia, with emphasis on the more common and more virulent bacteria encountered in hospital-acquired pneumonia and healthcare-associated pneumonia such as S. aureus, Pseudomonas aeruginosa, and other aerobic or facultative gram-negative bacilli [4,10-14,45].
These differences in pathogens are best explained by variations in setting (community, chronic care facility, or hospital), presentation (acute versus subacute onset), sampling method to avoid upper airway specimen contamination (transtracheal aspiration, protected brush catheter, or transthoracic aspiration versus expectorated sputum or routine bronchoscopy), specimen handling, quality of the microbiologic testing, and prior use of antimicrobials. Sputum specimens from patients with hospital-acquired pneumonia, even transtracheal aspiration specimens processed in specialized labs, show high yields of aerobic pathogens, only sometimes accompanied by obligate anaerobes . It also appears that the late sequelae of anaerobic lung infections, such as lung abscess, necrotizing pneumonia, and empyema, are less common than they were in the past for unknown reasons.
Pathophysiology — The standard teaching has been that the lower respiratory tract is normally sterile below the larynx so that specimens collected in such a way as to avoid contaminants from above that level (transtracheal aspiration, transthoracic aspiration, bronchoscopy with a protected brush) define pathology. However, more recent studies using culture-independent techniques have shown that there is a respiratory tract microbiome that extends from the nasal passages to the alveoli [47-49]. One possible hypothesis is that people are continually or frequently “micro-aspirating” leading to new and repeated inoculations . Bacterial aspiration pneumonia may result from larger inocula, greater pathogenicity of the aspirated microbes, local and/or systemic impairments in host defenses, or some combination of these.
Microbiology — Anaerobic bacteria were historically believed to be the dominant organisms in aspiration pneumonia and its sequelae (lung abscess and empyema), but subsequent studies have suggested that aerobic bacteria are probably at least as common and important clinically.
The role of anaerobes was identified in the 1970s in studies employing careful microbiologic techniques for the isolation of anaerobes [2,50-59]. Specimens for anaerobic culture were carefully obtained from the lower airways without contamination by upper airway bacteria by using transtracheal aspiration, flexible bronchoscopy with a shielded brush, transthoracic needle aspiration, or thoracentesis.
The major anaerobes isolated from pulmonary infections are Peptostreptococcus (gram-positive cocci in chains), Fusobacterium nucleatum (fusiform gram-negative bacilli), Fusobacterium necrophorum (long gram-negative bacilli), Prevotella, Bacteroides melaninogenicus (delicate gram-negative bacilli), and other Bacteroides spp [50-54].
Subsequent studies of aspiration pneumonias have found that aerobic bacteria may be more prevalent than anaerobic bacteria, particularly in patients without abscess formation, and mixed aerobic-anaerobic infections are common, as demonstrated by the following studies:
●A prospective study of 95 patients from a long-term care facility admitted to an intensive care unit with pneumonia and risk factors for aspiration found that gram-negative bacilli were the most common isolates (49 percent), followed by anaerobic bacteria (16 percent) and S. aureus (12 percent) . Aerobic gram-negative bacilli were recovered in conjunction with 55 percent of anaerobic isolates.
●In 212 Japanese patients with lung abscess, streptococci were the most common pathogens (60 percent of patients) and anaerobes were the second most common (26 percent) .
●Anaerobes appear to be even less common among patients with hospital-acquired aspiration pneumonia, where Streptococci, S. aureus, and gram-negative bacilli predominate [4,10-14,61].
Explanations for the higher rate of anaerobic infection in older studies include the assiduous culture techniques that were used, the presentation of patients later in the disease course, less use of antibiotics with anaerobic activity, and differences in the oropharyngeal microflora between otherwise healthy community dwelling and hospitalized adults [48,53,60,62,63].
Clinical features — The presenting findings in bacterial aspiration pneumonia are highly variable, depending upon the time the patient is seen during the course of their infection, the bacteria involved, and the status of the host. Compared with most cases of community-acquired pneumonia, the tempo of aspiration pneumonia involving anaerobes often evolves slowly. Fever is common; rigors and chills are not. There is usually an association with periodontal disease, and this complication is less common in patients with good dental hygiene and those who are edentulous. Hospital-acquired aspiration pneumonia often involves S. aureus or gram-negative bacilli, which commonly colonize the oral cavity of hospitalized patients.
Most patients present with the common manifestations of pneumonia, including cough, fever, purulent sputum, and dyspnea . Cases involving anaerobes usually evolve over a period of several days or weeks instead of hours [50,51]. Many patients have accompanying weight loss and anemia as common features of a more chronic process. With infections involving S. aureus or gram-negative bacilli, the tempo is much faster.
Clinical features, which are characteristic of bacterial aspiration pneumonia include:
●Indolent onset of symptoms; absence of rigors.
●A predisposing condition for aspiration, usually compromised consciousness due to drug abuse, alcoholism, or anesthesia; or dysphagia.
●Concurrent evidence of periodontal disease.
●Sputum that often has a putrid odor; this finding is often considered diagnostic of anaerobic infection, although evidence of anaerobic infection does not exclude the presence of clinically important aerobic pathogens.
●Failure to recover likely pulmonary pathogens with cultures of expectorated sputum in patients with suggestive clinical syndromes may suggest an anaerobic infection.
●Gram stain of appropriate specimens that show the characteristic morphologic features of anaerobes in large numbers, preferably in respiratory specimens that are uncontaminated by the flora of the upper airways. (See 'Microbiology' above.)
●Chest imaging showing involvement of the dependent portions of the lung or segments, an obstructed stricture or foreign body. Imaging with evidence of pulmonary necrosis with lung abscess and/or an empyema is consistent with an aspiration pneumonia, although not diagnostic of anaerobic infection.
With the slow tempo that characterizes lung infections involving anaerobes, many patients present later in their course with complications characterized by suppuration and necrosis, including lung abscess, necrotizing pneumonia, or empyema [50-52]. (See "Lung abscess in adults" and "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults".)
Evaluation — Bacterial aspiration pneumonia is suspected in patients with new or worsening respiratory impairment after an aspiration event or with risk factors for aspiration.
●Dysphagia – A history of coughing while eating or drinking is likely to indicate aspiration, but aspiration may also be silent [64,65]. Evaluation of dysphagia is described separately. (See "Approach to the evaluation of dysphagia in adults" and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management" and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)
●Microbiologic studies – Microbiologic studies are obtained depending on the severity of illness, as with community-acquired pneumonia (table 3). For patients who are hospitalized with aspiration pneumonia, whether the aspiration events occurred in the hospital or at home, we obtain blood cultures and sputum Gram stain and culture at a minimum. We suggest urine streptococcal antigen testing, sputum (or urine) Legionella testing, and a respiratory virus panel as well, given the difficulty differentiating pneumonia due to aspiration of gastric or oropharyngeal secretions alone versus pneumonia due to other causes. Molecular diagnostic tests for common bacterial and viral pathogens and their probable resistance profiles may be helpful where available. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Diagnosis'.)
For most hospitalized patients who are not critically ill, sputum studies are generally sufficient for the identification of clinically important aerobic organisms. Patients who require mechanical ventilation may be candidates for bronchoscopy to obtain lower airway samples.
Thoracentesis is generally indicated if parapneumonic pleural fluid is present. (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults".)
●Procalcitonin – Procalcitonin has not proven useful in determining the presence of bacterial lung infection after an aspiration event. In a study of 65 intubated patients with a witnessed aspiration, procalcitonin, measured on days 1 and 3, did not distinguish patients with positive lower respiratory cultures from those with negative cultures . (See "Procalcitonin use in lower respiratory tract infections".)
●Chest imaging – Occasionally the conventional chest radiograph will be negative early in the course, but chest computed tomography (CT) will identify the pneumonia [1,67]. Conversely, CT can often exclude the presence of pneumonia in patients with equivocal signs and symptoms . The main roles for CT are to identify and characterize abscesses, obstructing objects or lesions, and pleural disease including empyema.
Diagnosis — The diagnosis of bacterial aspiration pneumonia is generally clinical, based on the risk factors for aspiration, setting (home, hospital, chronic care facility), presenting clinical features, and chest imaging showing compatible opacities.
Treatment — In contrast with chemical aspiration pneumonitis, antibiotics are indicated for treatment of symptomatic aspiration pneumonia when bacterial infection is suspected. The management of complications of aspiration pneumonia, such as lung abscess and empyema, are discussed separately. (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults" and "Lung abscess in adults".)
Choice of regimen — Selection of an initial antibiotic regimen for bacterial aspiration pneumonia depends on the setting in which aspiration occurred (outpatient or hospital-acquired), clinical suspicion for anaerobic infection, severity of illness, and presence of antibiotic allergy. The initial regimen is adjusted as needed based on culture results and response to therapy.
●Community-acquired aspiration pneumonia – For patients with a clinical history that strongly suggests bacterial aspiration pneumonia, for example patients with dysphagia, altered mental status, compatible imaging (eg, dependent consolidative or ground glass opacities), and/or clinical signs of anaerobic pathogens (eg, putrid breath, severe periodontal disease, or dental caries), we suggest including anaerobic coverage in addition to targeting routine community acquired pneumonia (CAP) pathogens (eg, S. pneumoniae).
When the clinical history does not strongly suggest aspiration over other causes of CAP, we generally treat with a standard CAP regimen and do not add coverage for anaerobes (algorithm 1A-C). Note, however, that treatment regimens with and without anaerobic coverage for patients with suspected aspiration have not been compared in clinical trials. (See "Treatment of community-acquired pneumonia in adults who require hospitalization" and "Treatment of community-acquired pneumonia in adults in the outpatient setting".)
The choice of regimen varies with the severity of illness, risk factors for resistant pathogens, and antibiotic allergies :
•For outpatients with symptomatic community-acquired aspiration pneumonia and no risk factors for antibiotic resistant pathogens (table 4), we suggest oral amoxicillin-clavulanate (eg, 875 mg/125 mg twice daily or 2000 mg/125 mg twice daily). Dose adjustment may be needed in patients with impaired kidney function. We do not usually add coverage for atypical organisms with a macrolide or doxycycline when aspiration is strongly suspected. Moxifloxacin is an acceptable alternative for patients who cannot take amoxicillin/clavulanate or when additional treatment for atypical pathogens is indicated, but it is less well-studied in aspiration pneumonia.
•For patients with community-acquired aspiration pneumonia who require hospitalization but are not severely ill, we suggest ampicillin-sulbactam (1.5 to 3 g every six hours for those with normal kidney function). We prefer this regimen over cephalosporin-based regimens due to better anaerobic coverage. Alternatives for penicillin-allergic patients are discussed below and separately. (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Medical ward' and "Choice of antibiotics in penicillin-allergic hospitalized patients".)
•For patients who are severely ill, we suggest initiating intravenous therapy with imipenem, meropenem, or piperacillin-tazobactam; these agents cover virtually all anaerobes as well as most aerobic gram-negative bacilli (carbapenems more so than piperacillin-tazobactam). Coverage for Pseudomonas and methicillin-resistant S. aureus (MRSA) is added if the patient has risk factors for these infections (table 4). (See "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Intensive care unit'.)
•Alternative regimens based upon in vitro activity and limited clinical data are the combination of metronidazole (500 mg orally or IV three times daily) plus either amoxicillin (500 mg orally three times daily) or penicillin G (1 to 2 million units IV every 4 to 6 hours) or ceftriaxone (1 to 2 g IV daily). Metronidazole should not be used alone since monotherapy is associated with a failure rate of about 50 percent in the treatment of anaerobic pleuropulmonary infections [70,71]. The presumed reason for the high failure rates with metronidazole is its lack of activity against streptococci, which can be cultured in approximately 40 to 70 percent of cases.
●Hospital-acquired or healthcare-associated aspiration pneumonia – For hospital-acquired or healthcare-associated aspiration pneumonia, aerobic bacteria, especially gram-negative bacilli and S. aureus, are generally more important than anaerobes and are usually easily detected from adequate specimens [10,46,69]. For most patients, targeting these pathogens according to the guidelines for hospital acquired pneumonia (HAP) is sufficient (algorithm 2 and algorithm 3).
However, we add treatment for anaerobes when there is a higher likelihood that they are involved in the infection (eg, patients with frank aspiration, poor dentition, concomitant lung abscess or empyema, or persistent clinical deterioration despite treatment against aerobic bacteria). When there is a perceived need to treat anaerobic bacteria as well as resistant aerobic gram-negative bacilli (eg, in patients known to be colonized with resistant gram-negative bacilli or patients who have received IV antibiotics within the past 90 days), we suggest a carbapenem (imipenem, meropenem) or piperacillin-tazobactam since these agents cover virtually all anaerobes as well as most aerobic gram-negative bacilli (carbapenems more so than piperacillin-tazobactam). Before culture and susceptibility results are available, patients with risk factors for MRSA (eg, prior colonization) also require an agent with activity against MRSA (vancomycin or linezolid), but, if MRSA is not detected, then this agent should be discontinued.
The management of hospital-acquired pneumonia is discussed in detail separately. (See "Treatment of hospital-acquired and ventilator-associated pneumonia in adults".)
●Penicillin allergy – For out-patients who cannot tolerate penicillin, moxifloxacin (400 mg, once daily) is an appropriate choice; clindamycin (600 mg IV every eight hours) is an alternative, although it carries a greater risk of Clostridioides difficile infection.
Hospitalized patients who are able to take cephalosporins can take a combination of either ceftriaxone (1 or 2 g IV daily) or cefotaxime (1 or 2 g IV every 8 hours) with metronidazole (500 mg every 8 hours). Although the cephalosporins have not been studied for aspiration pneumonia, based on their in vitro activity and their established efficacy for community-acquired pneumonia, they are expected to be effective for aspiration pneumonia when used in combination with metronidazole. Carbapenems may be a reasonable alternative for some patients but have a broader spectrum.
Additional information about beta-lactam allergy is provided separately. (See "Allergy evaluation for immediate penicillin allergy: Skin test-based diagnostic strategies and cross-reactivity with other beta-lactam antibiotics" and "Immediate cephalosporin hypersensitivity: Allergy evaluation, skin testing, and cross-reactivity with other beta-lactam antibiotics" and "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Penicillin and cephalosporin allergy' and "Treatment of community-acquired pneumonia in adults who require hospitalization", section on 'Penicillin and cephalosporin allergy'.)
●Adjusting therapy when culture results are available – When aerobic pathogens are involved as primary pathogens or copathogens with anaerobes, the antibiotic regimen should be tailored based upon the respiratory aerobic culture and susceptibility results. As anaerobic culture and susceptibility results are often not available in clinical practice, decisions about the selection of antibiotic coverage for anaerobic copathogens must be made on the basis of older but still useful in vitro test patterns.
●Other antibiotics – Moxifloxacin has in vitro activity against respiratory pathogens including anaerobes, but it has not been adequately studied for aspiration pneumonia, and some data have suggested increasing rates of resistance of anaerobes to moxifloxacin. In addition, fluoroquinolones are associated with a higher risk of C. difficile infection than certain other antibiotic classes. (See 'Efficacy' below and "Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology", section on 'Antibiotic use'.)
Other agents commonly employed for pulmonary infections such as macrolides, tetracyclines, and cephalosporins have not been systematically studied in aspiration pneumonia.
All of the suggested regimens increase the risk of C. difficile infection, especially in patients with other risk factors such as hospitalization, advanced age, and severe illness. (See "Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology", section on 'Risk factors'.)
Duration of antibiotics and transition to oral therapy — The duration of antibiotics for aspiration pneumonia is arbitrary and not well studied. The usual duration of therapy for cases that are not complicated by cavitation or empyema is five days for community-acquired aspiration pneumonia and seven days for hospital-acquired aspiration pneumonia; shorter therapy may be effective but has not been adequately studied. Patients who are initially treated with parenteral antibiotics can be switched to oral antibiotics when they are improving clinically, hemodynamically stable, able to take oral medications, and have a normally functioning gastrointestinal tract . An appropriate choice for most patients is amoxicillin-clavulanate (875 mg orally twice daily). For patients who have a serious allergy (eg, an Ig-E mediated reaction) to penicillin, moxifloxacin (400 mg once daily) or clindamycin (450 mg orally three times daily) can be given.
Patients with associated pleural effusions should have a thoracentesis to exclude empyema, which often complicates pneumonia involving anaerobes. Patients with lung abscess need a longer course of antibiotics, usually until there is radiographic clearance or significant improvement, leaving only a small stable residual lesion. (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults" and "Lung abscess in adults", section on 'Duration of antibiotics'.)
As some patients initially thought to have aspiration pneumonia actually have chemical pneumonitis, it is appropriate to discontinue antibiotics if the signs and symptoms of pneumonia rapidly resolve.
Efficacy — Several regimens have been found to be effective in bacterial aspiration pneumonia, including ampicillin-sulbactam, amoxicillin-clavulanate, moxifloxacin, clindamycin, imipenem, and penicillin with metronidazole.
●A randomized trial evaluated the efficacy of clindamycin (600 mg twice daily), ampicillin-sulbactam (half dose, 1.5 g twice daily), ampicillin-sulbactam (full dose, 3 g twice daily), or imipenem (500 mg twice daily) in 100 older adult patients with aspiration pneumonia . All regimens were equally effective (cure rates ranged from 76 to 88 percent), but clindamycin was associated with a lower rate of posttreatment occurrence of methicillin-resistant S. aureus superinfection (0 of 25 compared with 5 to 8 of 25 in the other treatment arms). Diarrhea was not reported as an adverse effect in the clindamycin group, although it is known to be associated with C. difficile diarrhea.
●In an open-label, randomized trial that compared ampicillin-sulbactam with moxifloxacin in 96 patients with aspiration pneumonia or lung abscess, clinical resolution was noted in 66.7 percent of both groups . While this trial found that clinical cure rates with moxifloxacin were comparable to ampicillin-sulbactam, it has not been studied adequately to recommend it as a first-line agent for aspiration pneumonia, and the rate of resistance of anaerobes to this drug is increasing .
●Alternative regimens that appear effective include amoxicillin-clavulanate (studied in lung abscess)  and penicillin combined with metronidazole . As noted above, metronidazole should not be used alone but can be used if combined with a beta-lactam antibiotic.
●Clindamycin has been shown to be superior to penicillin alone in the treatment of necrotizing pneumonia and putrid lung abscess in terms of response rates and time to defervescence [76,77]. In one study of 37 patients with lung abscess or necrotizing pneumonia, the failure rate with clindamycin was 15 percent versus 44 percent with penicillin alone .
Outcomes — The cure rate for aspiration pneumonia with antibiotic therapy is 76 to 88 percent . Long-term follow-up studies of patients who survive severe aspiration pneumonia have revealed complete recovery in some patients and radiographic evidence of pulmonary fibrosis in others (image 3) [78,79].
MECHANICAL OBSTRUCTION — Aspiration pneumonia may involve fluid or particulate matter, which are not inherently toxic to the lung but can cause airway obstruction or reflex airway closure (image 4).
Fluids — Typical fluids that are aspirated and are not intrinsically toxic to the lungs include:
●Barium (image 5)
●Most ingested fluids including water
●Gastric contents with a pH exceeding 2.5
The most frequently observed form of fluid aspiration causing simple mechanical obstruction is that noted in victims of drowning. Patients at risk for mechanical obstruction are those who cannot clear the inoculum due to a profound neurologic deficit such as absence of a cough reflex or impaired consciousness.
Witnessed aspiration is treated with lateral head positioning and oropharyngeal suctioning; tracheal suctioning is performed, if an endotracheal tube is in place. If a subsequent chest radiograph does not show a new pulmonary opacity, no further therapy is required except for measures intended to prevent subsequent episodes of aspiration. In hospitalized patients, the most important preventive measure is semi-upright or upright positioning, particularly during feeding . (See 'Prevention' below.)
Solid particle aspiration — The severity of respiratory obstruction depends upon the relative size of the object that is aspirated and the caliber of the lower airways. Foreign body aspiration is most common in children from one to three years of age and among older adults . The usual objects recovered from the lower airways are peanuts, other vegetable particles, inorganic materials, and teeth [82-85]. Vegetable materials, including peanuts, are problematic because they are not visualized on plain chest radiographs. (See "Airway foreign bodies in adults".)
The clinical consequences depend upon the level of obstruction. Large objects that lodge in the larynx or trachea cause sudden respiratory distress, cyanosis, and aphonia that lead quickly to death if the obstruction is not immediately reversed. This is sometimes referred to as the "café coronary syndrome" because the symptoms simulate those of myocardial infarction and are often seen with aspiration of meat during restaurant dining . The suggested treatment is the Heimlich maneuver consisting of firm and rapid pressure applied to the upper abdomen in an effort to force the diaphragm up to dislodge the particle.
Aspiration of smaller particles causes less severe obstruction. These patients often present with an irritative cough, and chest radiograph shows atelectasis or obstructive emphysema with a cardiac shift and elevated diaphragm. When the obstruction is partial, unilateral wheezing may be appreciated.
For patients who are not able to expectorate particulate matter, the primary therapeutic modality is removal of the foreign object, usually with flexible or rigid bronchoscopy . Bacterial superinfection is a frequent complication when the obstruction or partial obstruction persists for more than one week [88,89]; the usual pathogens are anaerobic bacteria from the upper airways as described above. (See "Airway foreign bodies in adults".)
LIPOID PNEUMONIA — Exogenous lipoid pneumonia is most commonly caused by the aspiration of mineral oil when ingested to treat constipation or used intranasally as a vehicle for decongestants or as a home remedy for nasal dryness [90-93]; other causes include aspiration of industrial oils and nasal application of white petrolatum [94,95]. The most commonly affected patients are those at the extremes of age who have risk factors for aspiration. The result is either an inflammatory response with regional edema and intraalveolar hemorrhage or a "paraffinoma" with aspirated oils encapsulated by fibrous tissue (image 6) [94,96,97].
It has been hypothesized that exogenous lipoid pneumonia may be precipitated in some patients with e-cigarette or vaping product use associated lung injury (EVALI), due to the inhalation of heated oils as some investigators have noted lipid-laden macrophages in the bronchoalveolar lavage of some patients. (See "E-cigarette or vaping product use associated lung injury (EVALI)", section on 'Pathogenesis and risk factors'.)
Some patients (usually children) have an acute inflammatory reaction to oil aspiration and present acutely with cough, fever, and dyspnea. Other patients (usually older adults) have recurrent, asymptomatic events and are identified because of an abnormality noted on chest radiograph or present with a chronic cough, sometimes with sputum production, and dyspnea . Chest pain, hemoptysis, weight loss, and fever are less common. The chest radiograph typically reveals bilateral lower lung zone opacities that may be poorly-defined or mass-like [90,98].
The diagnosis of exogenous lipoid pneumonia is largely based on chest computed tomography (CT) findings, supported by a compatible history of exposure and bronchoalveolar lavage. Chest CT findings are often more extensive than expected based on symptoms and include ground glass opacities, thickened interlobular septa, crazy paving, and air bronchograms (image 6) [90,96]. Areas of consolidation containing foci of fat attenuation (<-30 Hounsfield units) are a characteristic feature [90,99].
Bronchoalveolar lavage (BAL) is often performed to evaluate for infection and malignancy. In lipoid pneumonia, BAL may reveal lipid-laden macrophages with large vacuoles that stain positive with Oil-Red-O stain, although this finding is nonspecific and may be falsely negative [90,100].
Treatment of exogenous lipoid pneumonia focuses on cessation of exposure to the oil source [91,98,101]. Many patients have sufficient improvement with avoidance that further therapy is not needed. For patients with more severe disease, a trial of systemic glucocorticoids may be a reasonable option, although the response has been mixed in observational studies [98,101-103]. For patients with severe respiratory impairment that is refractory to exposure cessation and a trial of systemic glucocorticoids, a few case reports describe improvement with whole lung lavage in patients with extensive lipoid pneumonia and severe respiratory impairment [101,103-105]. Whole lung lavage is used in pulmonary alveolar proteinosis and should only be undertaken in centers with experience in this technique. (See "Treatment and prognosis of pulmonary alveolar proteinosis in adults", section on 'Whole lung lavage'.)
PREVENTION — A number of interventions have been proposed to prevent aspiration, especially in older adult patients and stroke patients, although supportive data are limited:
●Semi-recumbent position – Data are mixed regarding the efficacy of a semi-recumbent (eg, 30 to 45 degree) position for preventing aspiration events [106,107], although we are in favor of using the semi-recumbent position for patients receiving enteral nutrition and those with reduced mental status.
●Enteral feeding – Percutaneous gastrostomy tubes and nasogastric tubes are efficient for delivering nutrition and oral medications in patients with dysphagia, but have not been shown to reduce the incidence of aspiration pneumonia compared with oral feeding [4,108,109]. Postpyloric tubes (eg, nasoduodenal, jejunal) have not been shown to reduce aspiration compared with gastric tubes.
●Speech and swallowing evaluation – For patients with impaired swallowing, particularly after stroke or intubation/mechanical ventilation, a full speech and swallowing evaluation is prudent. When a full evaluation is not possible, a water swallow test may help identify patients at increased risk of aspiration, although the test has a high false positive rate. (See "Oropharyngeal dysphagia: Clinical features, diagnosis, and management" and "Complications of stroke: An overview", section on 'Dysphagia'.)
●Thickened liquids and chin-down position – Thickened liquids may improve swallowing safety, but with the consequence of increased dehydration and reduced palatability and quality of life [1,110,111]. A potentially less effective alternative that patients may prefer is maintaining a chin-down position when swallowing liquids. A randomized trial compared chin-down position and oral feedings of two consistencies (nectar thickened or honey thickened) on the incidence of aspiration as assessed by videofluorography in 711 patients with dementia or Parkinson disease . Significantly more patients aspirated on thin liquids using the chin-down posture (68 percent) than when using nectar-thickened liquids (63 percent) or honey-thickened liquids (53 percent). However, a separate report evaluating the incidence of pneumonia at three months in a subset of 515 patients found no significant difference between patients randomized to chin-down position versus thickened liquids (9.8 versus 11.6 percent) . There was no control group, so one cannot determine if the interventions were effective compared with no intervention. There were numerically more episodes of the combined outcome of dehydration, urinary tract infection, and fever amongst patients randomized to thickened liquids (9 versus 5 percent, p = 0.055).
●Multicomponent strategy – A cluster randomized trial sought to determine whether a multicomponent strategy (including manual tooth/gum brushing plus 0.12 percent chlorhexidine oral rinse twice daily plus upright positioning during feeding) could reduce the incidence of pneumonia amongst 834 nursing home residents compared with usual care. The investigators found no significant difference in pneumonia rates in the intervention versus control arms (27.4 versus 23.5 percent) . It might have been difficult to detect a difference between the groups since upright positioning during feeding is practiced routinely in nursing homes , and oral hygiene is also a common part of usual nursing home care. However, a second cluster randomized trial amongst 2152 nursing home residents that focused on improving residents’ oral hygiene by improving staff members’ knowledge, attitudes, and practical skills in performing oral hygiene similarly found no difference in pneumonia rates over a two-year period (0.67 versus 0.72 pneumonias per 1000 resident-days) .
Techniques for the prevention of aspiration in hospitalized patients are discussed separately. (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Community-acquired pneumonia in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Aspiration pneumonia (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Aspiration pneumonia refers to the adverse pulmonary consequences that can sometimes result from aspiration of fluid, particulate exogenous substances, or endogenous secretions into the lower airways. (See 'Introduction' above and 'Definitions' above.)
●Syndromes commonly associated with aspiration include:
•Chemical pneumonitis, which refers to the aspiration of substances (eg, acidic gastric fluid) that cause an inflammatory reaction in the lower airways, independent of bacterial infection. (See 'Chemical pneumonitis' above.)
•Bacterial aspiration pneumonia, which refers to infection that results from inoculation of orogastric contents and bacteria. (See 'Bacterial pneumonia' above.)
•Mechanical obstruction, which refers to aspiration of fluid or particulate matter that leads to airway obstruction or triggers reflex airway closure. (See 'Mechanical obstruction' above.)
●These syndromes are not mutually exclusive and thus it can be challenging to classify individual cases. Understanding the risk factors for aspiration and the pathophysiology that underlies each of these syndromes can help guide care. (See 'Predisposing conditions' above.)
●All patients with an observed aspiration should have immediate pharyngeal or tracheal suction to clear fluids and particulate matter that may cause obstruction. (See 'Treatment' above.)
●Antimicrobial agents should be given following a witnessed aspiration in patients who develop new and persistent impaired oxygenation with associated inflammatory findings. Antibiotics are not necessary in patients that aspirate but rapidly recover. (See 'Treatment' above.)
●While anaerobes have traditionally been implicated in aspiration pneumonia, more recent data suggest aerobic bacteria predominate. Thus, it can be difficult to determine when to include an agent that targets anaerobes in the initial empiric treatment regimen. In general, we make this determination based on the degree of suspicion for aspiration, the clinical setting (community versus hospital-acquired), the severity of illness, and the patient’s clinical trajectory. (See 'Microbiology' above and 'Treatment' above.)
●For patients with a clinical picture that is strongly suggestive of aspiration pneumonia acquired in a community setting (eg, witnessed aspiration event, risk factors for aspiration, compatible imaging, subacute course, putrid breath), we select an antibiotic regimen that includes coverage for most pathogenic oral flora, including anaerobic bacteria. The specific regimen varies with the clinical setting, severity of illness, risk factors for resistant pathogens, and antibiotic allergies (see 'Choice of regimen' above):
•For outpatients, we suggest amoxicillin-clavulanate (eg, 875 mg/125 mg twice daily or extended release 2000 mg twice daily) (Grade 2C), with dose adjustments as needed for gastrointestinal intolerance or kidney impairment. We do not usually add a macrolide or doxycycline when aspiration is strongly suspected. Moxifloxacin is an acceptable alternative for patients who cannot take amoxicillin/clavulanate or when additional treatment for atypical pathogens is indicated, but it is less well-studied in aspiration pneumonia.
•For patients who require hospitalization but are not severely ill, we suggest ampicillin-sulbactam (1.5–3 g every six hours for those with normal kidney function) rather than a cephalosporin-based regimen due to better anaerobic coverage (Grade 2C). Modifications to the regimen may be needed for patients who are severely ill or have risk factors for Pseudomonas, methicillin resistant Staphylococcus aureus (MRSA), or other drug resistant pathogens (table 4).
●For patients with aspiration pneumonia acquired in a hospital setting, we generally target aerobic bacteria, because they are generally more important than anaerobes, using standard hospital acquired pneumonia (HAP) algorithms (algorithm 2 and algorithm 3). However, for patients with a witnessed aspiration, severe periodontal disease, imaging suggesting a necrotizing process, or failure to respond to an antibiotic regimen without anaerobic coverage, we add anaerobic coverage. Reasonable choices for most patients include imipenem, meropenem, or piperacillin-tazobactam. Modifications may be needed for patients with risk factors or evidence of MRSA or other resistant pathogens (table 4). (See 'Choice of regimen' above.)
●For outpatients who have a serious penicillin allergy (eg, an IgE-mediated reaction), moxifloxacin (400 mg, once daily) is an appropriate choice; clindamycin (600 mg IV every eight hours) is an alternative, although it carries a greater risk of Clostridioides difficile infection. For hospitalized penicillin-allergic patients with suspected anaerobic infection, potential alternatives include either a combination of a third, fourth, or fifth generation cephalosporin plus metronidazole (500 mg 3 times daily) or a carbapenem, depending on the type and severity of reactions to beta-lactams. Metronidazole is preferred over clindamycin in combination regimens because of concern for C. difficile; but metronidazole should not be used as monotherapy. (See 'Choice of regimen' above.)
●Patients who are initially treated with parenteral antibiotics can be switched to oral antibiotics when they are improving clinically, hemodynamically stable, able to take oral medications, and have a normally functioning gastrointestinal tract. For most such patients, we advise amoxicillin-clavulanate (875 mg orally twice daily). (See 'Duration of antibiotics and transition to oral therapy' above.)
●The duration of antibiotics for aspiration pneumonia is arbitrary and not well studied. The usual duration of therapy for cases that are not complicated by cavitation or empyema is five days for community acquired aspiration pneumonia and seven days for hospital acquired aspiration pneumonia. As some patients initially thought to have aspiration pneumonia actually have chemical pneumonitis, it is appropriate to discontinue antibiotics if the patient’s signs and symptoms of pneumonia rapidly resolve. (See 'Duration of antibiotics and transition to oral therapy' above.)
●Aspiration events may involve fluid or particulate matter (image 4), which are not inherently toxic to the lung but can cause airway obstruction or reflex airway closure. If the patient is not able to expectorate particulate matter, the primary therapeutic modality is removal with flexible or rigid bronchoscopy. (See 'Mechanical obstruction' above.)
●Exogenous lipoid pneumonia is most commonly caused by the aspiration of mineral oil, industrial oils, or white petrolatum when ingested or applied intranasally and subsequently aspirated. The diagnosis may be based on chest computed tomography; common features include ground glass opacities, thickened interlobular septa, crazy paving, air bronchograms, and areas of consolidation containing foci of fat attenuation. (See 'Lipoid pneumonia' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge John G Bartlett, MD, who contributed to an earlier version of this topic review.