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Ventilator-Associated Pneumonia
Overview
The term healthcare-associated pneumonia (HCAP) was defined as pneumonia in
nonhospitalized patients who had significant experience with the healthcare system. Such contact
could include (1) intravenous therapy for wound care within the preceding 30 days, (2) residence
in a long-term care facility, (3) hospitalization in an acute-care hospital within the preceding 90
days, and/or (4) outpatient treatment in a hospital or hemodialysis clinic within the preceding 30
days. These individuals were believed to be at an increased risk for infection with multidrugresistant (MDR) organisms because of such contact. [1] However, more recent studies have
indicated that many individuals who met the criteria for HCAP were not infected with MDR
pathogens. [2] The risk of infection with MDR organisms appears to depend much more on
specific risk factors of the given patient than on contact with various aspects of the healthcare
system. Patients who would have met the criteria for HCAP should not be empirically treated
with antibiotics to cover MDR bacteria unless they have valid risk factors for acquiring MDR
organisms (see below). [3]
Pneumonia is defined as "new lung infiltrates plus clinical evidence that the infiltrate is of an
infectious origin, which include the new onset of fever, purulent sputum, leukocytosis, and
decline in oxygenation." [4] Hospital-acquired pneumonia (HAP), or nosocomial pneumonia, is a
lower respiratory infection that was not incubating at the time of hospital admission and that
presents clinically 2 or more days after hospitalization. Pneumonia that presents sooner should be
regarded as community-acquired pneumonia. Ventilator-associated pneumonia (VAP) is defined
as pneumonia that presents more than 48 hours after endotracheal intubation.
Clinicians should understand that many of these findings are often shared with mimics of
nosocomial pneumonia, such as congestive heart failure (CHF), pulmonary emboli, pulmonary
hemorrhage, primary or metastatic lung carcinomas, leukemias/lymphomas, pulmonary drug
reactions, and radiation pneumonitis, among others. VAP refers to nosocomial pneumonia that
develops among patients on ventilators. [4, 1]
Pathophysiology
Inhalation, aspiration, and hematogenous spread are the 3 main mechanisms by which bacteria
reach the lungs. The primary route by which organisms enter the lower airways is aspiration of
oropharyngeal secretions into the trachea.
Primary inhalation pneumonia develops when these organisms bypass normal respiratory defense
mechanisms or when the patient inhales aerobic gram-negative organisms that colonize the upper
respiratory tract or respiratory support equipment.
Aspiration pneumonia is due to the aspiration of colonized upper respiratory tract secretions.
The stomach appears to be an important reservoir of gram-negative bacilli that can ascend and
colonize the respiratory tract. A prospective observational study found that patients who used
acid-suppressive medications were more likely to develop hospital-acquired pneumonia (HAP)
than were patients who did not (5% vs 2%). The risk for pneumonia was significantly increased
with proton pump inhibitors, but not with histamine 2blocking agents. [5]
Hematogenously acquired infections originate from a distant source and reach the lungs via the
bloodstream.
Etiology
The development of hospital-acquired pneumonia (HAP) represents an imbalance between
normal host defenses and the ability of microorganisms to colonize and then invade the lower
respiratory tract.
Because aerobic gram-negative bacilli (eg, Pseudomonas aeruginosa) are the major pathogens
associated with HAP, the pathophysiology of nosocomial pneumonia relates to the destructive
effect on lung tissue. Aerobic gram-negative pathogens may be divided into 2 categories. The
first category includes organisms that cause necrotizing pneumonia with rapid cavitation,
microabscess
formation,
blood-vessel
other
invasion,
nonnecrotizing
and
hemorrhage
gram-negative
bacilli
(eg, P
(eg, Serratia
P aeruginosa
Staphylococcus
aureus, including
methicillin-susceptible S
aureus (MSSA)
and
Klebsiella pneumoniae
Escherichia coli
Non-Enterobacteriaceae
bacteria
such
as S
marcescens,
Stenotrophomonas
Streptococcus pneumoniae and Haemophilus influenzae are recovered only in early-onset HAP.
Less-common pathogens associated with hospital-acquired pneumonia
The
following
are
less-common
pathogens
implicated
in
nosocomial
pneumonia
clusters/outbreaks:
Legionella species
Influenza A virus
P aeruginosa
S maltophilia
Acinetobacter species
These organisms are commonly recovered from respiratory secretions in patients with
VAP. [8] The recovery of a respiratory pathogen from respiratory secretions does not establish it as
the cause of nosocomial pneumonia. MSSA/MRSA frequently colonize respiratory secretions in
intubated patients but rarely, if ever, cause nosocomial pneumonia/VAP. In contrast,
MSSA/MRSA may cause community-acquired pneumonia (CAP) in those with influenza.
Anaerobic organisms are not important pathogens in nosocomial pneumonia. (See Differentials
in Nosocomial Pneumonia.)
Risk factors
The stomach appears to be an important reservoir of gram-negative bacilli that can ascend and
colonize the respiratory tract. A prospective observational study found that patients who used
acid-suppressive medications were more likely to develop hospital-acquired pneumonia (HAP)
than were patients who did not (5% vs 2%).
Further evaluation by drug class showed that the risk for pneumonia was significantly increased
with proton pump inhibitors, but not with histamine 2blocking agents. [5]
Compromised cardiac and lung function may further decrease their cardiopulmonary reserve.
Ventilator-associated barotrauma often decreases already compromised lung function. In
addition, it may alter chest radiographic appearances.
As mentioned above, early-onset HAP/VAP pneumonia (ie, hospital onset of CAP) expectedly
has a better prognosis than late-onset nosocomial pneumonia because the latter tends to be
associated with multidrug-resistant (MDR) organisms. [9, 10, 11, 12, 13]
Patient Prognosis
The prognosis in patients with hospital-acquired pneumonia (HAP) depends primarily on
preexisting underlying cardiopulmonary function and host defenses.
In
HAP/ventilator-associated
pneumonia
(VAP),
outcomes
usually
depend
on
risk
factors/comorbidities rather than on the initial empiric therapy. [14, 15, 16]
Lung hemorrhage
Bronchogenic carcinomas
Metastatic carcinomas
ARDS is usually readily diagnosable based on the appearance of small lung volumes due to
microatelectatic changes on the chest radiograph and the progressive and severe hypoxemia.
Little or no fever accompanies ARDS, unless it is due to acute pancreatitis.
Electrocardiography (ECG) and ventilation-perfusion scans help to exclude pneumonia mimics.
ECGs, cardiac enzymes, and Swan-Ganz readings may rule out left ventricular failure caused by
exacerbation of heart failure or new myocardial infarction.
Obtain other tests that are related to the possible underlying causes of the pulmonary
infiltrates; for example, if lupus pneumonitis is suspected, ask the patient about a
history of systemic lupus erythematosus (SLE) pneumonitis. Afterward, serologic
tests should be performed to assess for SLE.
Treatment Considerations
Guidelines on management of adults with hospital-acquired pneumonia (HAP) and ventilatorassociated pneumonia (VAP) by the Infectious Diseases Society of America and the American
Thoracic Society are as follows: [3]
In an effort to minimize patient harm and exposure to unnecessary antibiotics and reduce
the development of antibiotic resistance, the guidelines recommend that the antibiogram data
be used to decrease the unnecessary use of dual gram-negative and empiric methicillinresistantStaphylococcus aureus (MRSA) antibiotic treatment.
Short-course antibiotic therapy is recommended for most patients with HAP or VAP
regardless of microbial etiology, as well as antibiotic de-escalation.
However, the panel recognizes that invasive quantitative cultures will occasionally be
performed by some clinicians. For patients with suspected VAP whose invasive quantitative
culture results are below the diagnostic threshold for VAP, the guidelines suggest that
antibiotics be withheld rather than continued.
Suggest that patients with suspected HAP (non-VAP) be treated according to the results
of microbiologic studies performed on respiratory samples obtained noninvasively, rather than
being treated empirically.
For patients with suspected HAP/VAP, the guidelines recommend using clinical criteria
alone, rather than using serum procalcitonin (PCT) plus clinical criteria, bronchoalveolar
lavage fluid (BALF) sTREM-1 plus clinical criteria, or C-reactive protein (CRP) plus clinical
criteria to decide whether to initiate antibiotic therapy.
When empiric treatment that includes coverage for MSSA (and not MRSA) is indicated,
the guidelines suggest a regimen including piperacillin-tazobactam, cefepime, levofloxacin,
imipenem, or meropenem. Oxacillin, nafcillin, and cefazolin are preferred agents for
treatment of proven MSSA, but are not necessary for the empiric treatment of VAP if one of
the above agents is used.
For patients being treated empirically for HAP, prescribe an antibiotic with activity
against S aureus.
For patients with HAP who require empiric coverage for MRSA, vancomycin or linezolid
is recommended.
For patients with HAP/VAP due to P aeruginosa, the guidelines recommend that the
choice of an antibiotic for definitive (not empiric) therapy be based on the results of
antimicrobial susceptibility testing.
For patients with VAP or HAP, a 7-day course of antimicrobial therapy is recommended.
Antimicrobial therapy
Traditionally, nosocomial pneumonias have been treated for 7-14 days. However, ventilatorassociated pneumonia (VAP) (except due to nonfermenting gram-negative rods [eg, P
aeruginosa]) can be successfully treated in 7 days). If the patient receives appropriate
antimicrobial therapy for 2 weeks and does not respond (ie, improved infiltrates findings on
chest radiograph), initiate a diagnostic workup to detect nonbacterial infections (eg, herpesvirus
type 1 [HSV-1] pneumonitis) or noninfectious disease mimics (eg, bronchogenic carcinomas).
The specific pathogen that causes a given case of nosocomial pneumonia is usually unknown.
Therefore, empiric antimicrobial therapy is the only practical approach. These regimens should
be based on the local profile of organisms associated with hospital-acquired pneumonia (HAP)
and their antibiotic sensitivities.
Initial and definitive treatment of hospital-acquired pneumonia
MSSA should be covered unless the patient has risk factors for MRSA, including intravenous
antibiotic use within the preceding 90 days, exposure to a hospital unit where more than 20%
of S aureus isolates are MRSA, or a high risk of death (eg, need for ventilatory support due to
septic shock). Vancomycin or linezolid should be used to empirically cover MRSA.
For empiric coverage of MSSA, piperacillin-tazobactam cefepime, levofloxacin, imipenem, or
meropenem is preferred. In cases of proven MSSA infection, oxacillin, nafcillin, or cefazolin is
favored.
Double coverage against P aeruginosa should be provided in the empiric treatment of individuals
with HAP who are likely to have Pseudomonas and other gram-negative infections or who are at
a high risk of mortality (need for ventilatory support and/or septic shock). For all other cases,
single coverage of P aeruginosa is indicated. [9]
Patients located in units were more than 10%-20% of S aureus isolates are MRSA
The preferred antibiotics for treatment of MRSA infections include vancomycin and linezolid.
The recommended antibiotics for the treatment of suspected MSSA infections include
piperacillin-tazobactam, cefepime, levofloxacin, imipenem, and meropenem. When the pathogen
is confirmed as MSSA, the patient should be switched to oxacillin, nafcillin, or cefazolin.
The preferred antibiotics for treatment of MRSA VAP include vancomycin and linezolid.
A single antibiotic with activity against P aeruginosa should be administered, except in patients
with risk factors for multidrug-resistant (MDR) organisms, including the following:
The patient is located where more than 10% of gram-negative isolates are resistant
In general, aminoglycosides should be avoided in the treatment of VAP. This also holds true for
colistin. This recommendation is most likely based on poor penetration of these agents in the
lung tissue, in addition to the potential nephrotoxicity of aminoglycosides and the challenge in
achieving therapeutic blood levels in patients with fluctuating renal function.
In cases of HAP and VAP, antibiotics should be administered by either extended or continuous
infusion. Dosing needs to be based on an antibiotic blood levels and should also be weightbased, when applicable.
The use of inhaled antibiotic therapy should be generally limited to cases of VAP produced by
gram-negative bacilli that are sensitive only to aminoglycosides, colistin, or polymyxin B. These
antibiotics should also be administered systemically.
activity
and
low
resistance
potential.
Optimal
combinations
Failure to successfully wean the patient from the respirator (possibly because of a lack of
cardiopulmonary function or a superimposed process [eg, HSV-1 pneumonitis]) is a common
problem following intubation for nosocomial pneumonia.
HSV-1 pneumonitis develops in intubated patients who have unchanging or persistent pulmonary
infiltrates after 2 weeks of antimicrobial therapy. These patients usually have low-grade fevers
with variable degrees of leukocytosis. Demonstrating HSV-1 in samples of respiratory secretions
may establish the diagnosis.
Start treatment with acyclovir in patients diagnosed with HSV-1 infection; acyclovir decreases
hypoxemia and subsequently permits weaning of the patient from the respirator.
References
1. American Thoracic Society and the Infectious Diseases Society of America. Guidelines
for the management of adults with hospital-acquired, ventilator-associated, and
healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15.
171(4):388-416. [Medline].[Full Text].
2. Yap V, Datta D, Metersky ML. Is the present definition of health care-associated
pneumonia the best way to define risk of infection with antibiotic-resistant
pathogens?. Infect Dis Clin North Am. 2013 Mar. 27 (1):1-18. [Medline].
3. [Guideline] Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB,
et al. Management of Adults With Hospital-acquired and Ventilator-associated
Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of
America and the American Thoracic Society. Clin Infect Dis. 2016 Jul 14. [Medline].
4. Cunha BA. Pneumonia Essentials. 3rd ed. Royal Oak, Michigan: Physicians Press;
2010.
5. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER. Acid-suppressive medication use and
the risk for hospital-acquired pneumonia. JAMA. 2009 May 27. 301(20):21208. [Medline]. [Full Text].
6. Agodi A, Barchitta M, Cipresso R, et al. Pseudomonas aeruginosa carriage, colonization,
and infection in ICU patients. Intensive Care Med. 2007 Jul. 33(7):1155-61. [Medline].
7. Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilatorassociated bacterial pneumonia. Clin Infect Dis. 2010 Aug 1. 51 Suppl 1:S817. [Medline].
8. Bouza E, Torres MV, Radice C, et al. Direct E-test (AB Biodisk) of respiratory samples
improves antimicrobial use in ventilator-associated pneumonia. Clin Infect Dis. 2007 Feb
1. 44(3):382-7. [Medline].
34. Siempos II, Vardakas KZ, Manta KG, Falagas ME. Carbapenems for the treatment of
immunocompetent adult patients with nosocomial pneumonia. Eur Respir J. 2007 Mar.
29(3):548-60. [Medline].
35. Kullar R, Davis SL, Levine DP, Rybak MJ. Impact of vancomycin exposure on outcomes
in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for
consensus guidelines suggested targets. Clin Infect Dis. 2011 Apr 15. 52(8):97581. [Medline].
36. US Food and Drug Administration. FDA Drug Safety Communication: Serious CNS
reactions possible when linezolid (Zyvox) is given to patients taking certain psychiatric
medications. Available at http://www.fda.gov/Drugs/DrugSafety/ucm265305.htm.
Accessed: July 27, 2011.
37. Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R. Guidelines for preventing
health-care--associated pneumonia, 2003: recommendations of CDC and the Healthcare
Infection Control Practices Advisory Committee. MMWR Recomm Rep. 2004 Mar 26.
53:1-36.[Medline].
38. Cunha BA. Antibiotic selection is crucial for optimal empiric monotherapy of ventilatorassociated pneumonia. Crit Care Med. 2007 Aug. 35(8):1992-4. [Medline].
39. Cunha BA. The antibiotic treatment of community-acquired, atypical, and nosocomial
pneumonias. Med Clin North Am. 1995 May. 79(3):581-97. [Medline].
40. Cunha BA, Thekkel V, Schoch PE. Community-acquired versus nosocomial Legionella
pneumonia: Lessons learned from an epidemiologic investigation. Am J Infect Control.
2011 Dec. 39(10):901-3. [Medline].
41. Michalopoulos A, Fotakis D, Virtzili S, Vletsas C, Raftopoulou S, Mastora Z, et al.
Aerosolized colistin as adjunctive treatment of ventilator-associated pneumonia due to
multidrug-resistant Gram-negative bacteria: a prospective study. Respir Med. 2008 Mar.
102(3):407-12.[Medline].
42. Novosel TJ, Hodge LA, Weireter LJ, et al. Ventilator-associated pneumonia: depends on
your definition. Am Surg. 2012 Aug. 78(8):851-4. [Medline].
43. Wunderink RG, Woldenberg LS, Zeiss J, et al. The radiologic diagnosis of autopsyproven ventilator-associated pneumonia. Chest. 1992 Feb. 101(2):458-63. [Medline].