Aspiration Pneumonia Review Article - Amcli
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The n e w e ng l a n d j o u r na l of m e dic i n e
Review Article
Dan L. Longo, M.D., Editor
Aspiration Pneumonia
Lionel A. Mandell, M.D., and Michael S. Niederman, M.D.
A
spiration pneumonia is best considered not as a distinct entity From McMaster University, Hamilton,
but as part of a continuum that also includes community- and hospital- ON, Canada (L.A.M.); and Weill Cornell
Medical College, New York (M.S.N.). Ad-
acquired pneumonias. It is estimated that aspiration pneumonia accounts dress reprint requests to Dr. Mandell at
for 5 to 15% of cases of community-acquired pneumonia, but figures for hospital- lmandell@mcmaster.ca.
acquired pneumonia are unavailable.1 Robust diagnostic criteria for aspiration N Engl J Med 2019;380:651-63.
pneumonia are lacking, and as a result, studies of this disorder include heteroge- DOI: 10.1056/NEJMra1714562
neous patient populations. Copyright © 2019 Massachusetts Medical Society.
Aspiration of small amounts of oropharyngeal secretions is normal in healthy
persons during sleep, yet microaspiration is also the major pathogenetic mecha-
nism of most pneumonias.2 Large-volume aspiration (macroaspiration) of colo-
nized oropharyngeal or upper gastrointestinal contents is the sine qua non of
aspiration pneumonia. Variables affecting patient presentation and disease man-
agement include bacterial virulence, the risk of repeated events, and the site of
acquisition (nursing home, hospital, or community). According to this spectrum,
patients labeled as having aspiration pneumonia usually represent a clinical phe-
notype with risk factors for macroaspiration and involvement of characteristic
anatomical pulmonary locations. Aspiration syndromes may involve the airways or
pulmonary parenchyma, resulting in a variety of clinical presentations.3
This review focuses on aspiration involving the lung parenchyma, primarily
aspiration pneumonia and chemical pneumonitis. Aspiration of noninfectious
material such as blood or a foreign body is also important. Aspiration pneumonia
is an infection caused by specific microorganisms, whereas chemical pneumonitis
is an inflammatory reaction to irritative gastric contents. Our understanding of
the interaction between bacteria and the lung has improved. We examine this
improvement, along with changing concepts of the microbiology and pathogenesis
of aspiration pneumonia. We also examine the clinical features, diagnosis, treat-
ment, and prevention of both aspiration pneumonia and chemical pneumonitis, as
well as the risk factors.
Ch a nging Microbiol o gic a nd Patho gene t ic C oncep t s
of A spir at ion Pneumoni a
Our understanding of normal lower-airway microbiota in humans has evolved with
the use of targeted polymerase-chain-reaction studies, sequencing of bacterial 16S
ribosomal RNA genes, and metagenomics. A recent study of oral microbiota in
patients with acute stroke identified 103 different bacterial phylotypes, 29 of which
had not been reported previously.4 Whether these new microbes are pathogens is
uncertain.
The Human Microbiome Project has helped define the role that intestinal micro-
organisms play in the development of mucosal immunity and in the interplay
between health and disease. Studies of the lung microbiome have challenged our
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The n e w e ng l a n d j o u r na l of m e dic i n e
assumptions of lung sterility and of bacterial ac- such as glucocorticoids, have been shown in vi-
cess to the lungs through aspiration (microaspi- tro to promote the growth of S. pneumoniae and
ration or macroaspiration) and inhalation. Spe- certain gram-negative rods.13-16
cifically, genomic methods have defined a One hypothesis linking the airway microbiome
complex taxonomic landscape of bacteria in the with aspiration pneumonia is that illness may
lung and revealed the presence of diverse com- result in a change in the lung microbiota (dys-
munities of microbiota. We are still learning biosis), which may, in turn, interfere with or
about the role of the microbiome in health and impair pulmonary defenses. A macroaspiration
disease, as well as in the pathogenesis of pneu- event, particularly in a patient with risk factors
monia.5,6 In the healthy state, the immune tone for impaired bacterial elimination, such as re-
of the airways and alveoli appears to be calibrated duced consciousness or an impaired cough reflex,
by the bacteria constituting the lung microbiota, could then overwhelm the elimination side of the
an observation recently reported in both healthy immigration–elimination balance, further dis-
humans and experimental animal models.7,8 Con- rupting bacterial homeostasis and triggering an
cepts of virulence have also changed; virulence increase in a positive feedback loop leading to
is defined as “the relative capacity of a microor- acute infection.
ganism to cause damage to a host.”9 Infection is Bacteria may colonize various sites in the hu-
not simply the result of bacterial replication or of man oral cavity, such as the gingiva, dental plaque,
bacterial gene products; it is also a consequence and tongue.17,18 Pathogenic bacteria, including
of the host response, resultant inflammation, gram-negative species that are not seen in the
and tissue damage.9,10 normal host, may emerge in the elderly, as well
Models proposed to explain the possible role as in patients in nursing homes or hospitals and
of the lung microbiome in pneumonia include those with nasogastric tubes.19-21 Cleavage of cell-
the adapted island model of lung biogeography, surface fibronectin exposes receptors for gram-
effects of environmental gradients on lung micro- negative rods on underlying airway epithelial cells
biota (e.g., regional differences in oxygen ten- and is more closely correlated with host factors
sion and nutrient availability in the lungs), and such as acute illness than with the site of care.22
finally, pneumonia as an emerging phenomenon In the 1970s, anaerobes with or without aerobes
in the complex adaptive system of the lung micro- were the predominant pathogens in aspiration
bial ecosystem.11,12 The stability of the lung mi- pneumonia.23-26 More recently, there has been a
crobiome is probably maintained by a balance of shift to bacteria usually associated with commu-
immigration and elimination of bacteria and by nity- and hospital-acquired pneumonias, and
feedback loops. Immigration involves bacterial anaerobes are recovered less frequently.26 One
movement from the oropharynx to the lung pri- study of aspiration pneumonia in patients in the
marily by means of microaspiration, and elimi- intensive care unit showed that in community-
nation mainly occurs through ciliary clearance acquired cases, the main isolates were S. pneu-
and coughing. Negative and positive feedback moniae, Staphylococcus aureus, Haemophilus influenzae,
loops can suppress or magnify signals, respec- and Enterobacteriaceae, whereas gram-negative
tively, such as those for bacterial growth. An bacilli, including P. aeruginosa, were found with-
inflammatory event may lead to epithelial and out anaerobes in hospital-acquired cases.27 An-
endothelial injury, creating a positive feedback other study assessed the incidence of anaerobic
loop that can promote inflammation, disrupt bacteria in patients with ventilator-associated
bacterial homeostasis, and increase susceptibil- pneumonia and in those with aspiration pneu-
ity to infection. The complex adaptive system monia.28 Bacterial pneumonia was diagnosed in
model suggests that acute bacterial pneumonia 63 patients with ventilator-associated pneumonia
results from enhancement of a growth-promoting and in 12 patients with aspiration pneumonia.
signal by a positive feedback loop. This may re- Among patients with aspiration pneumonia, en-
sult in a rapid shift from a diverse microbial teric gram-negative organisms were isolated in the
mixture to dominance by a single species (e.g., patients with gastrointestinal disorders, whereas
Streptococcus pneumoniae or Pseudomonas aeruginosa).12 S. pneumoniae and H. influenzae predominated in
Various signaling molecules in humans, includ- those with community-acquired aspiration events.
ing neurotransmitters, cytokines, and hormones Only one anaerobic organism was found, and
652 n engl j med 380;7 nejm.org February 14, 2019
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Copyright © 2019 Massachusetts Medical Society. All rights reserved.Aspir ation Pneumonia
the authors questioned the need for anaerobic tion at the time of extubation continue to have
coverage in both ventilator-associated pneumo- this problem at the time of discharge.33
nia and aspiration pneumonia.28 Additional risks include degenerative neuro-
Studies of the elderly continue to show the logic diseases (multiple sclerosis, parkinsonism,
trend away from anaerobes. A study involving 95 and dementia) and impaired consciousness, par-
institutionalized elderly patients with severe ticularly as a result of stroke and intracerebral
aspiration pneumonia reported 67 pathogens.29 hemorrhage, which can also impair cough clear-
Gram-negative enteric bacteria accounted for ance. The frequency of stroke-associated pneu-
49% of the pathogens, anaerobes for 16%, and monia is related to the severity of neurologic
S. aureus for 12%. Aerobic gram-negative bacteria illness and its associated immune impairment,
were found in conjunction with 55% of anaero- with higher rates among patients requiring inten-
bic isolates. Another study, involving 62 elderly sive care than among those admitted to a stroke
hospitalized patients with aspiration pneumonia, unit.34 Impaired consciousness can also result
showed that of 111 bacteria identified, gram- from drug overdose and medications, including
negative bacilli and anaerobes each accounted narcotic agents, general anesthetic agents, certain
for 19.8% of the bacteria, and anaerobes and antidepressant agents, and alcohol (Fig. 2A).
aerobes together were found in 66.7% of pa- After adjustment for other risk factors, antipsy-
tients who died.30 It is unclear why the patho- chotic medications increased the risk of aspira-
gens have changed, but it may be due to a shift tion pneumonia by a factor of 1.5 in a study in-
in the demographic characteristics of patients volving 146,552 hospitalized patients.35 Enteral
and earlier sampling today than in the past. feeding can lead to high-volume aspiration, espe-
Prior studies often collected cultures later in the cially when associated with gastric dysmotility,
illness, often after the development of empyema poor cough, and altered mental status. In three
or lung abscess.1 This discussion does not apply studies of enteral feeding after a stroke in a total
to chemical pneumonitis, which unlike aspiration of more than 5000 patients, early tube feeding
pneumonia, is a noninfectious, inflammatory improved survival, as compared with no feeding,
response of the airways and pulmonary paren- and in the first 2 to 3 weeks after the stroke,
chyma to acidic gastric contents or bile acids.1,31 nasogastric tube feeding was associated with
improved survival and functional outcomes, as
compared with percutaneous enteral tube feed-
R isk Fac t or s
ing.36 Enteral feeding tubes are not currently
Aspiration is often the result of impaired swal- recommended for patients with dementia.37
lowing, which allows oral or gastric contents, Patients with multiple risks have increased
or both, to enter the lung, especially in patients rates of aspiration pneumonia, death, and other
who also have an ineffective cough reflex (Fig. 1). adverse outcomes. A meta-analysis of studies
Large-volume aspiration occurs with dysphagia; involving frail elderly patients showed that dys-
head, neck, and esophageal cancer; esophageal phagia increased the odds ratio for aspiration
stricture and motility disorders; chronic obstruc- pneumonia by a factor of 9.4, but when cerebro-
tive pulmonary disease; and seizures.1,3,32-41 In a vascular disease was also present, the odds ratio
case–control study involving elderly patients with rose to 12.9.38 In a study involving 1348 patients
pneumonia and healthy elderly controls, oropha- with community-acquired pneumonia, 13.8% of
ryngeal dysphagia increased the risk of pneumo- the patients were considered to be at risk for
nia (odds ratio, 11.9) and was present in nearly aspiration, and this subgroup of patients had a
92% of the patients who had pneumonia. Results higher 1-year mortality (hazard ratio, 1.73) and
of videofluoroscopic evaluation showed that increased risks of recurrent pneumonia (hazard
16.7% of the patients with pneumonia were able ratio, 3.13) and rehospitalization (hazard ratio,
to swallow safely, as compared with 80% of the 1.52) as compared with the rest of the study
controls.32 In extubated survivors of respiratory population.39 Similarly, a study involving 322
failure, dysphagia and aspiration are identified patients with community-acquired pneumonia
in at least 20% of patients. The frequency of identified the important risk factors for aspira-
swallowing dysfunction declines over time, but tion pneumonia as dementia (odds ratio, 5.20),
up to 35% of patients with swallowing dysfunc- poor performance status (odds ratio, 3.31), and
n engl j med 380;7 nejm.org February 14, 2019 653
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Pathogenesis and risk factors for the
development of pneumonia after
macroaspiration
Risk Factors
Impaired swallowing
Esophageal disease: dysphagia, cancer, stricture
Chronic obstructive pulmonary disease
Brain–swallowing axis
Neurologic diseases: seizures, multiple sclerosis,
parkinsonism, stroke, dementia Oropharyngeal contents
Mechanical ventilation extubation Gastric contents
Impaired consciousness
Neurologic disease: stroke
Cardiac arrest
Medications
General anesthesia
Alcohol consumption
Increased chance of gastric contents reaching the lung
Reflux
Tube feeding
Impaired cough reflex
Medications
Alcohol
Stroke
Dementia
Degenerative neurologic disease
Impaired consciousness
Figure 1. Pathogenesis of and Risk Factors for Pneumonia after Macroaspiration.
Macroaspiration can occur as a result of abnormalities in the swallowing mechanism or altered swallowing due to
dysfunction of the central nervous system. In patients with these disorders, oropharyngeal or gastric contents can
enter the lung. An impaired cough reflex increases the likelihood that aspirated material will reach the lung. Shown
are the disease processes that serve as risk factors for macroaspiration by impairing consciousness, swallowing,
and cough and by increasing the chance that gastric contents will reach the lung.
use of sleeping pills (odds ratio, 2.08).40 Those pneumonia is cardiac arrest. In a study involving
with two or more risk factors had an increased 641 patients with cardiac arrest, pneumonia de-
incidence of recurrent pneumonia and increased veloped within 3 days after the event in 65% of
30-day and 6-month mortality, with rates rising the patients.41 The presumed mechanism is aspi-
in parallel with the number of risk factors. The ration of gastric contents during resuscitation
relationship between distinct risk factors for (promoted by stomach ventilation and the resus-
macroaspiration and the frequency and outcome citation procedure) and inhalation of oral secre-
of aspiration pneumonia underscores the differ- tions during bag–valve–mask ventilation and in-
ence between aspiration pneumonia and tradi- tubation. When therapeutic hypothermia to 33°C
tional community-acquired pneumonia: patients was used after cardiac arrest, the odds ratio for
with traditional community-acquired pneumo- early-onset pneumonia rose by a factor of 1.9.41
nia have no associated increase in the risk of However, a target temperature of 36°C may be
aspiration. associated with a lower risk of pneumonia.42
An important clinical context for aspiration Some studies showed that the incidence of early-
654 n engl j med 380;7 nejm.org February 14, 2019
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Copyright © 2019 Massachusetts Medical Society. All rights reserved.Aspir ation Pneumonia
A B
C D
Figure 2. Characteristic Imaging Findings in Patients with Aspiration Pneumonia.
The chest radiograph in Panel A shows the findings in a 68-year-old man who presented with a several-week history
of cough, blood in the sputum, and a 6.8-kg weight loss but who was otherwise in generally good health. He had
extensive tooth decay and gingival inflammation. He did not drink alcohol or use illicit drugs but did take an anti-
depressant known to cause somnolence. The radiograph shows a cavitary infiltrate in the left lower lobe and an in-
filtrate in the left upper lobe. The radiograph in Panel B is from an 84-year-old man with small-bowel obstruction.
He had repeated episodes of vomiting, with the development of bilateral lung infiltrates, respiratory failure, and the
acute respiratory distress syndrome. Initial cultures were sterile, but 1 week later, he continued to have lung infil-
trates and sputum culture showed methicillin-resistant Staphylococcus aureus. The computed tomographic (CT)
scan in Panel C shows a cavitary infiltrate in the right upper lobe posteriorly in a 56-year-old man with cough after
tooth extraction performed with local anesthesia. He drank four beers per day. Bronchoscopic cultures revealed
Klebsiella pneumoniae. The CT scan in Panel D shows new bilateral infiltrates in posterior, gravity-dependent lung
segments in a 79-year-old man with dyspnea after upper endoscopy complicated by vomiting.
onset pneumonia decreased among patients re- Clinical features range from no symptoms to
ceiving systemic antibiotics at the time of car- severe distress with respiratory failure, and the
diac arrest.43 Two intervention studies involving clinical consequences may develop acutely, sub-
comatose patients showed a benefit of adminis- acutely, or slowly and progressively. Aspiration
tering prophylactic antibiotics for up to 24 hours into the lung can affect either the airway (caus-
after emergency intubation.44,45 ing bronchospasm, asthma, and chronic cough)
or the lung parenchyma. This discussion focuses
on aspiration into the lung parenchyma, which
Cl inic a l Fe at ur e s
can take the form of aspiration resulting in
Although macroaspiration is an essential feature chemical pneumonitis, aspiration of bland mate-
of aspiration pneumonia and chemical pneumo- rial (blood or the contents of tube feeding), or
nitis, many episodes are unwitnessed; therefore, aspiration resulting in bacterial pneumonia.
the magnitude of the exposure is often unknown. Aspiration pneumonia is usually acute, with
n engl j med 380;7 nejm.org February 14, 2019 655
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Copyright © 2019 Massachusetts Medical Society. All rights reserved.The n e w e ng l a n d j o u r na l of m e dic i n e
symptoms developing within hours to a few days and a pattern that is characteristic of acute respi-
after a sentinel event, although anaerobic aspira- ratory distress syndrome develops in up to 16.5%
tion may be subacute because of the less virulent of patients with witnessed aspiration, although
bacteria, and clinical features are difficult to the frequency rises if other risk factors (shock,
distinguish from those of other bacterial pneu- trauma, or pancreatitis) are also present 51
monias. In a study involving patients with pneu- (Fig. 2B). Low-pH aspirates are usually sterile, and
monia who were more than 80 years of age, bacterial infection is unusual initially, although
those with aspiration had a higher mortality, superinfection may develop subsequently.
higher serum sodium levels, and worse renal In most cases, neither chemical pneumonitis
function than patients without aspiration.46 In a nor aspiration pneumonia occurs with tube feed-
group of 53 patients with pneumonia and fluoro- ings or aspirated blood, since the aspirate pH is
scopically documented dysphagia, more patients usually high and uncontaminated by bacteria.
had bronchopneumonia than lobar pneumonia Although acid-suppressing therapy is associated
(68% vs. 15%), and 92% had posterior infiltrates.47 with an increased risk of community- or hospital-
Most patients with poor performance status had acquired pneumonia, which is related to gastric
diffuse and not focal infiltrates. Aspiration pneu- overgrowth by gram-negative bacteria, neutral-
monia is associated with higher mortality than ization of gastric pH may reduce the risk of
other forms of pneumonia acquired in the com- chemical pneumonitis.52 In a prospective cohort
munity (29.4% vs. 11.6%), a finding that may study involving 255 patients undergoing gastro-
have implications for hospitals that do not prop- intestinal endoscopy, the use of proton-pump
erly code its presence.48 In a survey of more than inhibitors or histamine H2 blockers was associ-
1 million patients in more than 4200 hospitals, ated with a significant reduction in the risk of
aspiration was documented in 4 to 26% of epi- gastric contents with a pH ofAspir ation Pneumonia
position during the event, or basal segments of with metronidazole failed in 5 of 11 cases of
the lower lobe, if the patient is upright during the lung abscess and in a randomized trial was less
event) (Fig. 2C and 2D). However, a chest radio- effective than clindamycin for anaerobic pulmo-
graph may be negative early in the course of nary infection.63,64
aspiration pneumonia. In a study involving 208 A prospective, randomized trial showed no
patients with pneumonia (more than 60% of significant differences among ampicillin–sulbac-
whom had aspiration), the chest radiograph was tam, clindamycin, and a carbapenem (panipenem–
negative in 28% of patients in whom pneumonia betamipron [not available in the United States])
was confirmed on computed tomography.55 One for the treatment of suspected aspiration pneu-
of the entities that can be confused with aspira- monia in elderly Japanese patients.65 A random-
tion pneumonia is negative-pressure pulmonary ized trial involving 96 patients compared moxi-
edema. It is important to consider this diagno- floxacin with ampicillin–sulbactam; both regimens
sis, which is accompanied by bilateral and gen- had clinical response rates of 66.7%.66 Anaerobes
erally symmetric lung infiltrates and is the result were isolated in 29.6% of patients with only lung
of breathing against a closed airway after general abscess. In those with only aspiration pneumo-
anesthesia, choking, or near drowning, all condi- nia, anaerobes were not found, and the most
tions that may also be accompanied by aspiration. frequent aerobes were Escherichia coli, Klebsiella
Although the diagnosis is usually clinical, pneumoniae, and P. aeruginosa (Fig. 2C).
some studies have used quantitative lung-lavage Antibiotic selection depends on the site of
cultures to distinguish bacterial from noninfec- acquisition (the community, a hospital, or a long-
tious (chemical and bland-aspiration) pneumo- term care facility) and risk factors for infection
nitis.56 Several investigations have studied bio- with multidrug-resistant pathogens. Risk factors
marker and biochemical measurements to predict include treatment with broad-spectrum antibiot-
bacterial infection after aspiration. A study involv- ics in the past 90 days and hospitalization for at
ing 65 intubated patients with risk factors for least 5 days. For most patients with community-
aspiration and a new lung infiltrate correlated acquired cases, treatment with ampicillin–sul-
quantitative bronchoalveolar-lavage cultures with bactam, a carbapenem (ertapenem), or a fluo-
serum procalcitonin levels.56 Measurement of roquinolone (levofloxacin or moxifloxacin) is
procalcitonin levels on days 1 and 3 did not dis- effective.3 In such patients, we suggest adding
tinguish the 32 patients with culture-positive clindamycin to another drug only when the risk
aspiration pneumonia from the 33 with culture- of predominantly anaerobic infection is high, as
negative pneumonitis. In studies of ventilated it is for patients with severe periodontal disease
patients, alpha-amylase levels (from salivary and and necrotizing pneumonia or lung abscess1
pancreatic sources) were elevated in airway secre- (Fig. 3 and Table 1). With mixed infection, elimi-
tions, at a frequency reflecting the number of risk nation of aerobic pathogens usually alters the
factors for aspiration, but the relevance of these local redox potential, eliminating anaerobes. For
findings to aspiration pneumonia and chemical hospital-acquired cases with a low risk of multi-
pneumonitis is not certain, and this is not a drug-resistant pathogens, a similar regimen may
method of value for diagnosis.57,58 be used. If resistance is a concern, broader-
spectrum treatment with piperacillin–tazobactam,
cefepime, levofloxacin, imipenem, or meropenem,
T r e atmen t
either singly or in combination, is required67
Aspiration Pneumonia (Fig. 3 and Table 1). In cases of multidrug-resis-
As documented pathogens have shifted from tant infection, an aminoglycoside or colistin may
anaerobes to aerobes, treatment regimens have be used as part of a combination regimen, with
also evolved. Even when anaerobes predominated the addition of vancomycin or linezolid if the
and penicillin was the drug of choice, penicillin- patient has documented nasal or respiratory
ase-producing anaerobes were reported.59,60 Com- colonization with methicillin-resistant S. aureus.
parative studies of anaerobic lung abscess and In a recent study involving comatose, mechan-
necrotizing pneumonia showed the superiority ically ventilated patients with aspiration, 43 of
of clindamycin, with penicillin failure attributed the 92 patients (46.7%) had bacterial aspiration
to resistant bacteroides species.61,62 Treatment pneumonia on the basis of bronchoscopic brush
n engl j med 380;7 nejm.org February 14, 2019 657
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Copyright © 2019 Massachusetts Medical Society. All rights reserved.658
Aspiration events including aspiration
pneumonia and chemical pneumonitis
Hospital-acquired or long-term
Community-acquired
care–acquired
Abnormal chest Abnormal chest
The
Clear chest radiograph Clear chest radiograph
radiograph radiograph
If poor dental health, If normal dental If mild-to-moderate If severe illness If no risk of MDR, If there is a risk If mild-to-moderate If severe illness
n engl j med 380;7
treat with ampicillin– health, treat with illness, withhold anti- (patients who are treat with ampicillin– of MDR, treat with illness, withhold (patients who are
sulbactam, ampicillin– biotics and observe intubated or in septic sulbactam, piperacillin– antibiotics and intubated or in septic
amoxicillin– sulbactam, shock), treat amoxicillin– tazobactam, observe shock), treat
clavulanate, amoxicillin– according to risks clavulanate, cefepime, according to risks
fluoroquinolone clavulanate, based on dentition fluoroquinolone levofloxacin, based on dentition
nejm.org
(moxifloxacin), fluoroquinolone and MDR and (levofloxacin, carbapenem and MDR and
carbapenem (levofloxacin, reassess in 48–72 hr; moxifloxacin), (meropenem, reassess in 48–72 hr;
n e w e ng l a n d j o u r na l
(ertapenem) moxifloxacin), consider bron- carbapenem imipenem) consider bron-
The New England Journal of Medicine
choscopy and BAL
of
carbapenem choscopy and BAL (ertapenem), plus either
(ertapenem), to guide decision ceftriaxone aminoglycoside to guide decision
ceftriaxone or colistin
February 14, 2019
Figure 3. An Algorithmic Approach to Antibiotic Therapy for Aspiration Pneumonia.
Copyright © 2019 Massachusetts Medical Society. All rights reserved.
m e dic i n e
For patients with suspected aspiration pneumonia, the decision about antibiotic therapy is dictated by the site of acquisition: community, hospital, or long-term care facility. Antibi-
otics are given to patients who have an aspiration event and an abnormal chest radiograph, although even with an initially normal radiograph, antibiotics are given to those with se-
vere illness (i.e., illness characterized by shock or requiring intubation). If chemical pneumonitis is suspected, antibiotics are not initially recommended, even with an abnormal ra-
diograph, unless the patient is severely ill; in patients with mild-to-moderate illness and an abnormal radiograph, the recommendation is to withhold antibiotics and reassess the
patient in 48 hours. Therapy is directed at the pathogens likely to be present in the patient at the time of aspiration, determined on the basis of the site of acquisition, with risk fac-
tors for resistant pathogens taken into consideration. Patients with severe illness are treated on the basis of risks associated with their dental health and multidrug resistance
(MDR). Routine treatment for anaerobic pathogens is not needed in patients with normal dental health but should be considered in those with poor dental health (e.g., clindamycin
in patients with poor dental health and necrotizing pneumonia or lung abscess). If the site of acquisition is the community, outpatient treatment with amoxicillin–clavulanate, moxi-
floxacin, levofloxacin, or clindamycin can be administered orally. In the hospital, treatment is usually administered intravenously, but oral options are available for select patients; if
there is nasal or respiratory colonization with methicillin-resistant S. aureus, the addition of vancomycin or linezolid can be considered. BAL denotes bronchoalveolar lavage.
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samples.68 The investigators suggested that rou- Table 1. Antibiotic Treatment of Aspiration Pneumonia.*
tine antibiotic treatment should be started only if
bacterial infection is suspected but may be dis- Drug Dose, Schedule, and Route of Administration
continued if bronchoscopic cultures are negative. Ampicillin–sulbactam 1.5–3 g every 6 hr, intravenous
On the basis of data from studies of commu- Amoxicillin–clavulanate 875 mg twice daily, oral
nity-acquired pneumonia and hospital-acquired
Piperacillin–tazobactam 4.5 g every 8 hr or 3.375 g every 6 hr, intravenous
or ventilator-associated pneumonia, we suggest
Ceftriaxone 1–2 g once daily, intravenous
5 to 7 days of treatment for patients with a good
clinical response and no evidence of extrapulmo- Cefepime 2 g every 8–12 hr, intravenous
nary infection, and longer treatment for those Ertapenem 1 g once daily, intravenous
with necrotizing pneumonia, lung abscess, or em- Imipenem 500 mg every 6 hr or 1 g every 8 hr, intravenous
pyema. In the case of lung abscess or empyema, Meropenem 1 g every 8 hr, intravenous
drainage for diagnostic and treatment purposes Levofloxacin 750 mg once daily, intravenous or oral
may be needed. The choice of therapy should
Moxifloxacin 400 mg once daily, intravenous or oral
take into account potential drug-related adverse
events, including Clostridium difficile colitis and Clindamycin 450 mg three or four times daily, oral; or 600 mg
every 8 hr, intravenous
selection of antibiotic resistance. More data are
Gentamicin or tobra 5–7 mg/kg once daily, intravenous
needed to identify the best antibiotic regimens mycin†
for aspiration pneumonia and to determine the
Amikacin† 15 mg/kg once daily, intravenous
duration of treatment. No randomized, controlled
Colistin‡ 9 million IU per day in two or three divided
trials have shown a role for glucocorticoids in doses, intravenous
the routine treatment of aspiration pneumonia,
Vancomycin† 15 mg/kg every 12 hr, intravenous
and we do not recommend their use.
Linezolid 600 mg every 12 hr, intravenous or oral
Chemical Pneumonitis
* Doses are for patients with normal renal function.
Initial treatment of gastric aspiration requires air- † The dose should be adjusted to a trough level of less than 1 mg per liter for
way maintenance, management of airway edema gentamicin and tobramycin, a trough level of less than 4 mg per liter for ami-
kacin, and a trough level of 10 to 15 μg per milliliter for vancomycin, with renal
or bronchospasm, and minimization of tissue function taken into consideration in all cases.
damage. Depending on the severity of the pneu- ‡ A loading dose of 6 million to 9 million IU can be administered.
monitis and the extent of care required, treatment
may include suctioning, bronchoscopy, intuba-
tion, mechanical ventilation, and intensive care. formed (Table 2). Medications known to pro-
Routine adjunctive treatment with glucocorticoids mote aspiration and interfere with swallowing
is not recommended, and antibiotics are not should be avoided, including sedatives, antipsy-
needed routinely unless the patient is taking acid- chotic agents, and for some at-risk patients, anti-
suppressing medication or has small-bowel ob- histamines.35 Aspiration-prevention efforts focus-
struction. In mild-to-moderate cases, we recom- ing on ventilator-associated pneumonia are not
mend withholding antibiotics even if there is discussed here.
radiographic evidence of an infiltrate, monitoring For patients with swallowing disorders, par-
clinical and radiographic findings, and reassess- ticularly after stroke, a full speech and swallow-
ing after 48 hours. In more serious cases, how- ing evaluation is necessary. Efforts should be
ever, antibiotics should be started empirically, and made to promote oral rather than enteral tube
the decision to continue antibiotic therapy for feeding, with the use of a mechanical soft diet
more than 2 to 3 days should be guided by the with thickened liquids rather than pureed food
clinical course. and thin liquids. In addition, “nutritional reha-
bilitation” with swallowing exercises and early
mobilization may help patients with dysphagia
Pr e v en t ion
and may prevent recurrence of aspiration pneu-
Postoperative chemical pneumonitis can be min- monia.69 Patients should receive enteral feeding
imized by ensuring that the patient has fasted in a semirecumbent rather than supine position
for at least 8 hours and has abstained from clear to minimize the risk of gastric aspiration. For
liquids for at least 2 hours before surgery is per- patients with oropharyngeal dysphagia, an effort
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Table 2. Prevention of Aspiration Pneumonia.
A meta-analysis of five randomized, controlled
trials involving nonventilated patients at risk for
Recommended in the appropriate clinical setting aspiration pneumonia showed that oral care with
Antibiotic therapy for 24 hr in comatose patients after emergency intubation chlorhexidine or mechanical oral cleaning was
No food for at least 8 hr and no clear liquids for at least 2 hr before elective effective in preventing pneumonia (odds ratio,
surgery with general anesthesia 0.4 to 0.6).76 However, chlorhexidine use is con-
To be considered in the appropriate clinical setting troversial and may be associated with increased
Swallowing evaluation after stroke and after extubation from mechanical mortality among ventilated patients, possibly as
ventilation a result of toxic effects if chlorhexidine is aspi-
Preference for angiotensin-converting–enzyme inhibitors for blood-pressure rated into the lung.77 In a randomized study in-
control after stroke volving 252 patients, supplemental nutrition plus
Oral care with brushing and removal of poorly maintained teeth daily oral cleaning reduced the frequency of
Feeding in a semirecumbent position for patients with stroke pneumonia (7.8%, vs. 17.7% with usual care;
Not yet recommended; more data needed
P = 0.06).78 In a case–control study involving 539
patients undergoing surgery for esophageal can-
Swallowing exercises for patients with dysphagia after stroke
cer, postoperative pneumonia developed in 19.1%
Oral chlorhexidine in patients at risk for aspiration
of the patients. Lack of preoperative oral care,
including tooth scaling, mechanical cleaning,
should be made to keep the patient’s chin down and tooth extraction if necessary, was an impor-
and head turned to one side during feeding and tant risk factor.79 Despite these promising find-
to encourage swallowing of small volumes, mul- ings, a cluster-randomized study involving 834
tiple swallows, and coughing after each swallow.33 nursing home patients, with a mean observation
In a study involving comatose patients, the risk time of slightly more than 1 year, showed no
of aspiration pneumonia was reduced by keep- benefit of a comprehensive oral care program,
ing patients in either the prone or semirecum- which included manual tooth and gum brushing,
bent position.70 chlorhexidine mouth washes, and upright posi-
The role of nasogastric tubes in preventing tioning during feeding, with radiographic evi-
aspiration pneumonia is uncertain. In a study dence of the development of pneumonia in 25%
involving 1260 patients, the 630 patients with a of the patients.80
nasogastric tube in place did not have more as- Antibiotic administration for up to 24 hours
piration events during endoscopic observation of in comatose patients who have been intubated
swallowing than the 630 patients without a naso- on an emergency basis has shown a benefit in
gastric tube.71 Postpyloric feeding is not superior two trials. An open, randomized, controlled study
to gastric feeding, and monitoring of postfeed- involving 100 intubated, comatose patients with
ing residual volume may not minimize the risk stroke or head injury showed that 1.5 g of cefu-
of aspiration.3,72 For patients with stroke, particu- roxime given every 12 hours for two doses re-
larly Asian patients, the use of angiotensin-con- duced the occurrence of pneumonia, particularly
verting–enzyme (ACE) inhibitors to control blood early-onset pneumonia.44 Control patients receiv-
pressure can reduce the risk of aspiration pneu- ing antibiotics at the time of intubation had lower
monia, possibly by elevating substance P levels, pneumonia rates than those not receiving anti-
which promotes cough and improves the swal- biotics. A subsequent cohort study showed that a
lowing reflex.73,74 In a meta-analysis of data from single dose of antibiotic (ceftriaxone or ertapenem)
8693 patients with stroke, patients who received administered within 4 hours after intubation was
ACE inhibitors had a reduced risk of aspiration, effective in preventing early-onset but not late-
as compared with patients who did not receive onset pneumonia in comatose patients,45 includ-
ACE inhibitors (odds ratio, 0.6).74 Cilostazol, an ing the 25% of patients who were intubated on
antiplatelet agent that may have a similar effect an emergency basis after cardiac arrest.
on substance P, has also been shown to prevent
pneumonia after stroke.34 C onclusions
In the prevention of aspiration pneumonia, a
focus on oral hygiene has yielded an inconsistent Aspiration pneumonia is an important illness
benefit, possibly because of study design issues.75 that is difficult to accurately diagnose and to
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Copyright © 2019 Massachusetts Medical Society. All rights reserved.Aspir ation Pneumonia
distinguish from other aspiration syndromes Dr. Mandell reports receiving fees for serving on a data moni-
toring committee from Bayer and Polyphor, fees for serving on a
and community- and hospital-acquired pneumo-
data and safety monitoring board from Cubist Pharmaceuticals
nias. The diagnosis should be considered in the and Shionogi, and lecture fees from Daiichi Sankyo; and Dr. Nieder-
appropriate clinical settings in patients with man, receiving consulting fees from Thermo Fisher, Paratek,
known risk factors for aspiration and character- Nabriva, Melinta, and Shionogi, advisory fees from Pfizer, and
grant support and consulting fees from Merck and Bayer. No other
istic clinical and radiographic findings. Aspira- potential conflict of interest relevant to this article was reported.
tion pneumonia is treated with antibiotics as Disclosure forms provided by the authors are available with
required but not with glucocorticoids. Preventive the full text of this article at NEJM.org.
We thank Dr. Robert P. Dickson, Division of Pulmonary and
measures should be used for patients at risk for Critical Care Medicine, University of Michigan, for his assistance
aspiration. and thoughtful comments on an earlier version of the manuscript.
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