Ventilator-Associated Pneumonia in Neonates: An Update

Jeffery S. Garland
Neoreviews 2014;15;e225
DOI: 10.1542/neo.15-6-e225

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Article

infectious diseases

Ventilator-Associated Pneumonia in
Neonates: An Update
Jeffery S. Garland, MD,
SM*

Author Disclosure
Dr Garland has
disclosed no financial
relationships relevant

Practice Gaps
1. Accurately determining the specific organism responsible for ventilator-associated
pneumonia is challenging in neonates.
2. Few randomized trials have been conducted to evaluate measures to prevent
ventilator-associated pneumonia in neonates.
3. It is not known whether a level or head-elevated position influences the risk of
ventilator-associated pneumonia (VAP).

to this article. This

commentary does not

Abstract

contain a discussion of

Health-careassociated infections affect neonatal morbidity and mortality, as well as

length of stay and hospital costs. Ventilator-associated pneumonia (VAP) accounts
for 6.8% to 32.2% of these infections. Low birthweight, duration of mechanical ventilation, opiate treatment for sedation, frequent suctioning, and reintubation have all
been shown to increase the risk of VAP. Both Gram-positive and Gram-negative organisms that originate from endogenous or exogenous sources are responsible for
VAP. Accurately diagnosing VAP in neonates is challenging because procedures such
as tracheal aspirate culture and Gram-stain have low sensitivity, specicity, and positive
predictive value. Although several authors have shown that bronchial aspirates through
nonbronchoscopic bronchoalveolar lavage improve diagnostic accuracy, further studies are needed to investigate the diagnostic value and safety prole of these procedures.
Very few randomized trials have been conducted in neonates to evaluate methods to
prevent VAP, and thus most neonatal VAP prevention recommendations are based on
adult trials. This review summarizes the epidemiology, pathogenesis, diagnosis, and
treatment of VAP and touches on a number of practical steps to prevent VAP in
neonates.

an unapproved/
investigative use of
a commercial product/
device.

Objectives
1.
2.
3.
4.
5.

After completing this article, the reader should be able to:

Describe the risk factors for neonatal ventilator-associated pneumonia (VAP).

Describe the current methods used to diagnose neonatal VAP.
List the most common organisms responsible for neonatal VAP.
Explain initial treatment of neonatal VAP.
Outline steps to prevent neonatal VAP.

Introduction
The Centers for Disease Control and Prevention (CDC) denes ventilator-associated
pneumonia (VAP) as an episode of pneumonia in a patient
who requires a device to assist or control respiration through
a tracheostomy or endotracheal tube within 48 hours before
Abbreviations
the onset of the infection. (1) Although the exact incidence
of VAP is difcult to determine, VAP may be responsible for
CDC: Centers for Disease Control and Prevention
as many as one-third of the health-carerelated infections in
NHSN: National Healthcare Safety Network
neonates. (2)(3)(4)(5)(6) The present review summarizes
SDD: selective digestive tract decontamination
the epidemiology, suspected pathogenesis, diagnosis, treatVAP: ventilator-associated pneumonia
ment, and strategies for the prevention of VAP in neonates.
*Director of Neonatal-Perinatal Research, Wheaton Franciscan HealthcareSt Joseph Hospital, Milwaukee, WI.

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infectious diseases

ventilator-associated pnuemonia

Epidemiology
Increased permeability of the skin and mucous membranes, decreased complement activity, lower concentrations of immunoglobulins, and an immature and
dysregulated immune system together increase the risk
of health-careacquired infections in critically ill neonates. Multiple physiologic mechanisms optimally protect
the lung parenchyma from infection, including: anatomical barriers; the cough reex; the tracheobronchial mucociliary lining and secretions; and cell-mediated and
humoral immunity, including the phagocytic functions
of alveolar macrophages and neutrophils. If these defenses are impaired, absent, or overcome by a high
inoculum of organisms or those of unusual virulence,
pneumonitis ensues.
Data from the CDCs National Healthcare Safety Network (NHSN) (20062008) at 304 participating hospitals revealed VAP rates of 2.36 and 2.08 per 1,000
device-days among neonates weighing less than 750 g
and between 750 and 1,000 g, respectively. (7) The true
rate of neonatal VAP is difcult to establish. Radiographic
identication of neonatal pneumonia is difcult, compromised by evolving parenchymal changes due to bronchopulmonary dysplasia and frequent episodes of atelectasis.
Diagnostic procedures commonly used in adults to diagnose VAP (eg, bronchoscopic bronchoalveolar lavage,
protected specimen brushing) are
rarely used in the neonatal intensive
care unit (NICU), in part due to the
small size of neonatal endotracheal
tubes. Retrospective cohort studies
conducted at single institutions report higher VAP rates (10.952 infections per 1,000 ventilator-days)
than NHSN data. (2)(8)(9)(10)
(11)(12)(13) Risk factors reported
to be signicantly associated with
VAP among ventilated neonates
also vary from study to study. Low
birthweight, prolonged mechanical
ventilation, opiate treatment for sedation, frequent suctioning and reintubation, bloodstream infection,
and steroid use have all been noted
to be associated with increased risk
of VAP. (14)(15)

Pathogenesis
Organisms responsible for VAP
can originate from endogenous or

exogenous sources (Figs 1 and 2). A number of investigators have described the role of pharyngeal and
subglottic secretions in the development of VAP in
adults. (16)(17)(18)(19)(20) Contaminated oral or
gastric secretions of intubated, ventilated adult patients
can pool above the cuff of the endotracheal tube, leak
around the cuff, and enter the lower respiratory tract. Because neonates are ventilated with uncuffed endotracheal
tubes, they are likely at greater risk for aspiration of contaminated oral or gastric secretions. Within the rst 48
hours of mechanical ventilation, (21)(22) Gram-positive
oral organisms begin to colonize the trachea and endotracheal tube, and Gram-negative bacilli generally colonize
endotracheal tubes in place for longer than 48 hours.
One study provided some evidence that neonatal positioning may inuence the incidence of lower respiratory tract
bacterial colonization. (23) In this study, tracheal colonization was less common among neonates placed in a lateral
position compared with neonates nursed in a supine
position.
Organisms responsible for VAP may also originate
from the stomach, although the exact role gastric ora
plays in the pathogenesis of VAP has been questioned.
(24)(25) Torres et al (26) noted that VAP in adults
was more common among supine patients compared
with semi-recumbent patients. Farhath et al (27) noted

Figure 1. Endogenous sources of organisms responsible for ventilator-associated

pneumonia (VAP). (Courtesy of Walt Earhart, Wheaton Franciscan Healthcare. From:
NeoreviewsPlus
August 2010, Question 8, by AAP.)

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infectious diseases

ventilator-associated pnuemonia

that can lead to VAP. Gram-negative

organisms, which often colonize endotracheal tubes, are frequently
noted in the ora that colonize the
hands of caregivers. (30)(31)

Microbiology
In adult and pediatric patients in
whom reliable cultures can be obtained, Staphylococcus aureus and
Gram-negative organisms (Pseudomonas
aeruginosa, Escherichia coli, Klebsiella
pneumoniae, Enterobacter species, and
Acinetobacter species) are the most
common pathogens responsible for
VAP. Gram-negative organisms were
noted in 94% of tracheal aspirates
from neonates who had VAP in a cohort reported by Apisarnthanarak
et al. (13) S aureus was recovered
from w25% of cases, and multiple
Figure 2. Exogenous sources of organisms responsible for ventilator-associated organisms were recovered from airpneumonia (VAP). (Courtesy of Walt Earhart, Wheaton Franciscan Healthcare. From: way secretions in 58% of cases. In a reNeoreviewsPlus
August 2010, Question 8, by AAP.)
cent work by Cernada et al, (32)
gram-negative organisms (particularly
P
aeruginosa)
were
responsible for 62% of VAP
that pepsin, a marker for gastric contents, was detected in
cases.
This
study
diagnosed
VAP by using bronchoalveolar
the trachea of 92% of a cohort of ventilated neonates, suglavage
with
a
blind
protected
catheter; with this techgesting that contaminated gastric contents could make
nique,
only
3
(16.7%)
of
18
neonates
had polymicrobial
their way into the trachea of ventilated neonates. Based
infections.
on trials that used rigorous culturing techniques and standard denitions of VAP, oropharyngeal colonization likely
plays a greater role than aspiration of contaminated gastric
secretions. (22) Although previous bloodstream infection
has been identied as a risk factor for VAP, these infections
do not seem to be the source of VAP. (13) Bloodstream
infections and translocation of bacteria from the gastrointestinal tract are also believed to be an uncommon source
of endogenous organisms responsible for VAP.
Exogenous sources may also be responsible for the
pathogens causing VAP (Fig 2). Shortly after intubation,
bacteria can coat the surface of endotracheal tubes and
become enveloped within a biolm produced by the microbes. This biolm can serve as an exogenous source of
organisms responsible for VAP. In a study of adult patients, Adair et al (28) noted that 70% of patients who
have VAP had the same pathogens isolated from endotracheal biolms and tracheal secretions. Pathogens that
contaminate ventilator circuits, airway suctioning equipment, humidiers, nebulizers, and, most importantly, caregivers hands (29) are sources of exogenous contamination

Diagnosis
The primary controversy regarding VAP in neonates is
the criteria used to establish the diagnosis. (33) The
CDCs NHSN VAP criteria included radiographic, clinical, and microbiologic elements. (1) The difculty in obtaining noncontaminated microbiologic specimens that
meet quantitative denitions for infection led the CDC
to include a purely clinical denition of VAP for infants
aged 1 year, as shown in Table 1. The criteria have
not been validated in neonates, and they are often open
to subjective interpretation because they overlap with
a number of disease processes. As of January 1, 2014,
the CDC and NHSN no longer analyze data for neonatal
pneumonia because the diagnosis is so subjective according to a CDC working group. (34) Neonatal units may
still perform internal VAP surveillance, but the data will
not be analyzed by the NHSN.
Microbiologic criteria for VAP are shown in Table 2.
(1) Note that these criteria presume that pulmonary
specimens are obtained by using invasive testing, such
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ventilator-associated pnuemonia

CDC Alternate Criteria for Diagnosis of VAP Among Infants Age

1 Year
Table 1.

Radiographic criteriaa
New or progressive infiltrate and persistent infiltrate
Consolidation
Cavitation
Pneumatoceles
Clinical criteria
Worsening gas exchange (eg, oxygen desaturations, increased oxygen requirements, increased ventilator demand)
And three of the following
Temperature instability
Leukopenia (<4,000 WBC/mm3) or leukocytosis (>15,000 WBC/mm3) and left shift (>10% band forms)
New onset of purulent sputum or change in character of sputum, or increased respiratory secretions or increased suctioning
requirements
Apnea, tachypnea, nasal flaring with retraction of chest wall or nasal flaring with grunting
Wheezing, rales, or rhonchi
Cough
Bradycardia (<100 beats per minute) or tachycardia (>170 beats per minute)
CDCCenters for Disease Control and Prevention; VAPventilator-assisted pneumonia; WBCwhite blood cell count.
a
In the absence of underlying conditions, one denitive chest radiograph is acceptable. Among infants who have underlying conditions, two or more serial
denitive radiographs are required. For neonates, underlying pulmonary or cardiac disease may include respiratory distress syndrome, bronchopulmonary
dysplasia, pulmonary edema, chronic obstructive pulmonary disease, and/or congenital heart disease.

as those obtained with bronchoalveolar lavage or through

a protected specimen brush, frequently used to diagnose
VAP in adults. As mentioned earlier, both techniques
need to be performed through a bronchoscope, thus precluding their widespread use in intubated neonates.
Kksal et al (35) used invasive testing with nonbronchoscopic bronchoalveolar lavage to obtain specimens from
ventilated neonates with suspected pneumonia. Ninety
percent of the 40 neonates who had clinically diagnosed

VAP had positive lavage culture results. Sensitivity, specicity, and positive and negative predictive values were
90%, 90%, 70%, and 97%, respectively. The presence of
intracellular bacteria in polymorphonuclear cells on
Giemsa-stained smears was signicantly higher in neonates who have VAP compared with colonized neonates.
There were no signicant complications, but because the
procedure is blind to what actually is being cultured, it is
possible that the samples were taken more proximally

CDC Microbiologic Criteria for Diagnosis of Common Bacterial or

Fungal VAP
Table 2.

In addition to radiographic and clinical criteria, at least one of the following is present:
Positive growth in blood culture not related to another source of infection
Positive growth in culture of pleural fluid
Positive quantitative culture from minimally contaminated lower respiratory tract specimen (eg, BAL, protected specimen
brushing)
5% BAL-obtained cells contain intracellular bacteria on direct microscopic examination (eg, Gram-stain)
Histopathologic examination shows at least one of the following indications of pneumonia:
- Abscess formation or foci of consolidation with intense PMN accumulation in bronchioles and alveoli
- Positive quantitative culture of lung parenchyma
- Evidence of lung parenchyma invasion by fungal hyphae or pseudohyphae
BALbronchoalveolar lavage; CDCCenters for Disease Control and Prevention; PMNpolymorphonuclear leukocyte; VAPventilator-assisted
pneumonia.

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infectious diseases

from the trachea. Cernada et al (32) used a blind protected catheter to assist in diagnosing pneumonia in another cohort of neonates who had suspected VAP. They
did not report sensitivity or specicity of the procedure. A
limitation of both of these studies is that they were compared with clinically diagnosed VAP and not with a gold
standard such as a lung biopsy or tissue sample. Larger
trials need to be conducted to assess the diagnostic value
and safety prole of the procedures.
In many NICUs, tracheal aspirate cultures and Gramstains are commonly used to try to establish the diagnosis
of VAP in neonates. Tracheal aspirates have low sensitivity, specicity, and positive predictive value for diagnosing VAP because it is difcult to distinguish between
tracheal colonization and true pneumonia. (36) However,
tracheal colonization of the airway with Gram-negative
bacteria has been associated with adverse outcomes.
(37) Tracheal aspirates from neonates who have suspected VAP may play a role in helping to identify organisms colonizing the airway and aid in the choice
of appropriate antibiotic therapy. This nding may
be of value, given evidence that there is a greater risk of
death in adults from VAP if their pneumonia was initially
treated with the wrong antibiotic. (38)(39) Furthermore,
a sterile tracheal aspirate culture may also be of value in
that sterile cultures have a high negative predictive value
for VAP. (40)
Routine use of clinical biomarkers such as C-reactive
protein, soluble triggering receptor expressed on myeloid type 1 cells, or procalcitonin to help identify VAP
has not been supported in ventilated adults. (41) Studies have not been conducted to determine the utility
of biomarkers for the diagnosis of VAP in neonatal
patients.

Treatment
There are no clear consensus guidelines for the optimal
treatment of neonatal VAP. Most treatment recommendations are taken from adult guidelines and are supported
by epidemiologic principles. Initial treatment should include broad empiric therapy, preferably informed by local
bacterial colonizing and antimicrobial sensitivity data.
Local NICU antibiotic combinations for the empiric
treatment of late-onset bloodstream infections should
be used for suspected VAP, unless individual infant
colonizing information is available. Empiric treatment
will often include an antipseudomonal agent such as
piperacillin/tazobactam or ticarcillin/clavulanate to provide coverage of both Gram-negative and Gram-positive
organisms. Carbapenems may be more appropriate for

ventilator-associated pnuemonia

initial empiric therapy if local ora include extensive betalactamaseproducing organisms. Additional Gram-negative
coverage with an aminoglycoside is controversial but may
be indicated when bacteremia is suspected or signicant
systemic symptoms are present. If systemic symptoms
are absent and the blood culture result is negative, deescalating therapy by discontinuing the aminoglycosides
may be appropriate. Gram-positive coverage for methicillinresistant S aureus may be required if local epidemiologic
data dictate its use.
Overall, multiple risk factors (eg, prolonged mechanical ventilation, previous antibiotic exposure, multisystem illness) place neonates at increased risk for
multidrug-resistant VAP, and there is no validated
means of assessing VAP severity or VAP improvement
after treatment, as there is in adults. Because of these
factors, most neonates who have VAP will receive a full
course of empiric broad-spectrum antibiotic therapy
unless specic culture results allow for the use of more
narrow-spectrum therapy. (14)(15)

Prevention of VAP
The CDC (42) and the American Thoracic Society (43)
have published guidelines for the prevention of healthcareassociated pneumonia. Bundles bring together
a number of evidence-based practices that, when applied
as a single intervention (ie, the bundle), may result in improvement that is greater than single evidence-based
practices. (44)(45)(46) These recommendations address
the following specic items.

Management of secretions and techniques for

suctioning
Adult VAP prevention bundles often include 30 to 45
of head elevation to prevent aspiration of contaminated
oropharyngeal and gastric uids. The results of Aly
et al (23) and Farhath et al (27) suggest that gravity
may be used to prevent pathogens from gaining entry into the lower respiratory track of ventilated neonates.
Farhath et al showed that a majority of ventilated neonates aspirated gastric pepsin, perhaps providing support
for elevating the head of the neonatal bed, but this study
did not evaluate the association between the presence
of pepsin in the trachea and VAP. Aly et al evaluated
tracheal colonization in supine and lateral-nursed ventilated infants and found that the lateral-nursed infants
had less tracheal bacterial colonization; however, the
study did not specically assess VAP. The optimum position to nurse neonates for the prevention of VAP needs
further investigation.
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The CDC recommends that secretions be cleared

from above the cuff of the endotracheal tube anytime
the tube is repositioned or removed. (42) Neonates are
usually cared for with uncuffed endotracheal tubes. Suctioning the oropharynx around the endotracheal tube before adjusting it or removing it may reduce risk of
microaspiration of contaminated oropharyngeal secretions. Although close systems are frequently used for
the care of ventilated neonates, they may present the potential for bacterial contamination if pooled secretions in
the lumen are reintroduced into the respiratory tract with
repeated suctioning. Conversely, closed suctioning could
potentially reduce environmental contamination of the
respiratory tract. In a study of 133 ventilated neonates
randomized to a closed or open suction system, no difference was noted in tracheal colonization patterns between
groups, nor were there differences in VAP rates among
treatment groups. Physiologic disruptions were less with
the closed suction systems, and NICU nurses indicated
that these systems were easier to use than open suction
systems. (47) At minimum, separate suctioning equipment should be used for tracheal and oral secretions.
One recent study evaluated a low-sodium, physiologically based solution for suctioning of ventilated neonates. (48) A signicant reduction in the VAP rate was
demonstrated after normal saline for airway suctioning
was replaced by the novel solution for airway suctioning.
Further trials with the solutions are necessary to conrm
these results. Finally, respiratory tubing should be
drained away from ventilated infants to prevent aspiration
of potentially contaminated condensate. (49) Breathing
circuits do not need routine changing unless they become
visibly soiled or they malfunction. (42)

Extubation procedures
VAP reduction bundles often recommend sedation vacations to assess extubation readiness. Because many
centers use minimal or no sedation for ventilated neonates, sedation vacations are uncommon in most units.
Assessing for extubation readiness should be done on
a daily basis. Noninvasive measures such as nasal continuous positive airway pressure and nasal prong ventilation
may help to reduce VAP rates. (9) Reintubation after extubation should be avoided if possible because of the increased risk of VAP associated with reintubation. (50)

Gastrointestinal and oropharyngeal

interventions.
Manipulation of gastrointestinal contents is part of adult
VAP prevention. Although H2-blocker treatment is frequently a standard intervention in bundles to prevent

VAP in adults, current data do not support such treatment in ventilated neonates. In addition, the use of
H2-blockers is associated with increased risk of late-onset
fungal infection and necrotizing enterocolitis among very
low birthweight NICU infants. (51)(52)
Selective digestive tract decontamination (SDD) with
enteral nonabsorbable antimicrobials and antimicrobials
applied directly to the oropharynx can decrease gastrointestinal colonization and potentially reduce respiratory
tract infections from microaspiration of gastrointestinal
organisms. CDC guidelines (42) offer no recommendation for the selective decontamination of the digestive
tract. In a nonrandomized prospective trial of ventilated
neonates, those who underwent SDD with polymyxin E,
tobramycin, and nystatin had fewer nosocomial infections
of intestinal origin. (53) VAP episodes were not reported
separately. SDD should be evaluated further before it is
considered for neonates outside of clinical trials. The
use of probiotic treatment to inuence neonatal gastrointestinal colonization has focused on reducing late-onset
bloodstream infections and necrotizing enterocolitis,
but one recent trial of Lactobacillus reuteri administration
also demonstrated the effect of probiotic administration
on the incidence of VAP. (54)
The CDC recommends a comprehensive oral hygiene
program in patients at high risk for health-careassociated
pneumonia. (42) Although several groups have noted
a reduction in VAP among adult patients treated with
oral chlorhexidine gluconate decontamination, the
CDC makes no recommendation for the use of an oral
chlorhexidine gluconate rinse for the prevention of
VAP in ill patients. Chlorhexidine gluconate is not approved for neonates less than age 2 months. Because neonates do not have gingivitis or the dental diseases adults
often have, oral care may not provide the benet it does
in adult patients. Until further data are available, adhering
to the recommendation of the American Dental Association to wipe off the gums and keep the mouth clean after
feedings and when needed seems prudent.

Infection control measures

Hand hygiene is likely the most important infection control intervention in health-care settings to reduce person
person transmission of bacteria. Pathogens responsible
for neonatal VAP are carried on health-care workers
hands and in the infants gastrointestinal tracts. Respiratory equipment can become colonized with these organisms. (55) Thorough hand-washing before and after
contact with respiratory equipment should reduce
cross-contamination between patients.

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Figure 3. Relationship between preventative measures and pathogenesis of ventilator-associated pneumonia (VAP). (Adapted from

Garland JS. Strategies to prevent ventilator-associated pneumonia in neonates. Clin Perinatol. 2010;37(3):638. Copyright 2010,
with permission from Elsevier.)

Changes in endotracheal tube design have decreased

incidence of VAP in adults. A hole in the dorsal aspect
of endotracheal tubes above the inated cuff allows for
clearing of subglottic secretions. The CDC recommends
the use of such tubes in ventilated adults. (42) Unfortunately, such tubes are not available for neonates. Silvercoated endotracheal tubes, which are not available for
neonates, have also been shown to reduce VAP in adults
by reducing biolm formation and bacterial colonization.
Figure 3 summarizes how practical preventative interventions relate to the steps in the pathogenesis of VAP.
Improved diagnostic criteria and surveillance techniques for VAP in the neonatal population need to be es-

tablished before the effectiveness of these strategies can

be accurately assessed.

American Board of Pediatrics NeonatalPerinatal

Content Specifications
Know the pathogenesis and causative
agents in an infant in whom neonatal
pneumonia is suspected.
Plan the clinical, imaging, and laboratory
features and the management of an
infant in whom neonatal pneumonia is
suspected.

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References
1. Centers for Disease Control and Prevention. Criteria for dening
nosocomial pneumonia. Available at: http://www.cdc.gov/nhsn/
PDFs/pscManual/6pscVAPcurrent.pdf. Accessed January 31, 2014
2. van der Zwet WC, Kaiser AM, van Elburg RM, et al. Nosocomial infections in a Dutch neonatal intensive care unit: surveillance
study with denitions for infection specically adapted for neonates.
J Hosp Infect. 2005;61(4):300311
3. Gaynes RP, Edwards JR, Jarvis WR, Culver DH, Tolson JS,
Martone WJ; National Nosocomial Infections Surveillance System.
Nosocomial infections among neonates in high-risk nurseries in the
United States. Pediatrics. 1996;98(3 pt 1):357361
4. Drews MB, Ludwig AC, Leititis JU, Daschner FD. Low birth
weight and nosocomial infection of neonates in a neonatal intensive
care unit. J Hosp Infect. 1995;30(1):6572
5. Ford-Jones EL, Mindorff CM, Langley JM, et al. Epidemiologic
study of 4684 hospital-acquired infections in pediatric patients.
Pediatr Infect Dis J. 1989;8(10):668675
6. Hemming VG, Overall JC Jr, Britt MR. Nosocomial infections
in a newborn intensive-care unit. Results of forty-one months of
surveillance. N Engl J Med. 1976;294(24):13101316
7. Hocevar SN, Edwards JR, Horan TC, Morrell GC, Iwamoto M,
Lessa FC. Device-associated infections among neonatal intensive
care unit patients: incidence and associated pathogens reported to
the National Healthcare Safety Network, 2006-2008. Infect
Control Hosp Epidemiol. 2012;33(12):12001206
8. Yuan TM, Chen LH, Yu HM. Risk factors and outcomes for
ventilator-associated pneumonia in neonatal intensive care unit
patients. J Perinat Med. 2007;35(4):334338
9. Hentschel J, Brngger B, Stdi K, Mhlemann K. Prospective
surveillance of nosocomial infections in a Swiss NICU: low risk of
pneumonia on nasal continuous positive airway pressure? Infection.
2005;33(5-6):350355
10. Cordero L, Ayers LW, Miller RR, Seguin JH, Coley BD.
Surveillance of ventilator-associated pneumonia in very-low-birthweight infants. Am J Infect Control. 2002;30(1):3239
11. Pessoa-Silva CL, Richtmann R, Calil R, et al. Healthcareassociated infections among neonates in Brazil. Infect Control Hosp
Epidemiol. 2004;25(9):772777
12. Su BH, Hsieh HY, Chiu HY, Lin HC, Lin HC. Nosocomial
infection in a neonatal intensive care unit: a prospective study in
Taiwan. Am J Infect Control. 2007;35(3):190195
13. Apisarnthanarak A, Holzmann-Pazgal G, Hamvas A, Olsen
MA, Fraser VJ. Ventilator-associated pneumonia in extremely
preterm neonates in a neonatal intensive care unit: characteristics,
risk factors, and outcomes. Pediatrics. 2003;112(6 pt 1):1283
1289
14. Garland JS. Strategies to prevent ventilator-associated pneumonia in neonates. Clin Perinatol. 2010;37(3):629643
15. Cernada M, Brugada M, Golombek S, Vento M. Ventilatorassociated pneumonia in neonatal patients: an update. Neonatology.
2014;105(2):98107
16. Kollef MH. The prevention of ventilator-associated pneumonia. N Engl J Med. 1999;340(8):627634
17. de Latorre FJ, Pont T, Ferrer A, Rossell J, Palomar M, Planas
M. Pattern of tracheal colonization during mechanical ventilation.
Am J Respir Crit Care Med. 1995;152(3):10281033
18. George DL, Falk PS, Wunderink RG, et al. Epidemiology of
ventilator-acquired pneumonia based on protected bronchoscopic
sampling. Am J Respir Crit Care Med. 1998;158(6):18391847

19. Mahul P, Auboyer C, Jospe R, et al. Prevention of nosocomial

pneumonia in intubated patients: respective role of mechanical
subglottic secretions drainage and stress ulcer prophylaxis. Intensive
Care Med. 1992;18(1):2025
20. Valls J, Artigas A, Rello J, et al. Continuous aspiration of
subglottic secretions in preventing ventilator-associated pneumonia.
Ann Intern Med. 1995;122(3):179186
21. Cardeosa Cendrero JA, Sol-Violn J, Bordes Bentez A, et al.
Role of different routes of tracheal colonization in the development
of pneumonia in patients receiving mechanical ventilation. Chest.
1999;116(2):462470
22. Feldman C, Kassel M, Cantrell J, et al. The presence and
sequence of endotracheal tube colonization in patients undergoing
mechanical ventilation. Eur Respir J. 1999;13(3):546551
23. Aly H, Badawy M, El-Kholy A, et al. Randomized, controlled
trial on tracheal colonization of ventilated infants: can gravity prevent
ventilator-associated pneumonia? Pediatrics. 2008;122(4):77774
24. Bonten MJ, Gaillard CA, van Tiel FH, Smeets HG, van der
Geest S, Stobberingh EE. The stomach is not a source for
colonization of the upper respiratory tract and pneumonia in ICU
patients. Chest. 1994;105(3):878884
25. Craven DE, Steger KA, Barber TW. Preventing nosocomial
pneumonia: state of the art and perspectives for the 1990s. Am J
Med. 1991;91(3B):44S53S
26. Torres A, Serra-Batlles J, Ros E, et al. Pulmonary aspiration of
gastric contents in patients receiving mechanical ventilation: the
effect of body position. Ann Intern Med. 1992;116(7):540543
27. Farhath S, He Z, Nakhla T, et al. Pepsin, a marker of gastric
contents, is increased in tracheal aspirates from preterm infants who
develop bronchopulmonary dysplasia. Pediatrics. 2008;121(2):
e253e259
28. Adair CG, Gorman SP, Feron BM, et al. Implications of
endotracheal tube biolm for ventilator-associated pneumonia.
Intensive Care Med. 1999;25(10):10721076
29. Alcn A, Fbregas N, Torres A. Hospital-acquired pneumonia:
etiologic considerations. Infect Dis Clin North Am. 2003;17(4):
679695
30. van Ogtrop ML, van Zoeren-Grobben D, Verbakel-Salomons
EM, van Boven CP. Serratia marcescens infections in neonatal
departments: description of an outbreak and review of the
literature. J Hosp Infect. 1997;36(2):95103
31. Szab D, Filetth Z, Szentandrssy J, et al. Molecular
epidemiology of a cluster of cases due to Klebsiella pneumoniae
producing SHV-5 extended-spectrum b-lactamase in the premature
intensive care unit of a Hungarian hospital. J Clin Microbiol. 1999;
37(12):41674169
32. Cernada M, Aguar M, Brugada M, et al. Ventilator-associated
pneumonia in newborn infants diagnosed with an invasive bronchoalveolar lavage technique: a prospective observational study.
Pediatr Crit Care Med. 2013;14(1):5561
33. Baltimore RS. The difculty of diagnosing ventilator-associated
pneumonia. Pediatrics. 2003;112(6 pt 1):14201421
34. Centers for Disease Control and Prevention. Surveillance for
ventilator-associated events. Available at: http://www.cdc.gov/
nhsn/acute-care-hospital/vae/. Accessed March 3, 2014
35. Kksal N, Hacimustafaolul M, elebi S, Ozakin C. Nonbronchoscopic bronchoalveolar lavage for diagnosing ventilatorassociated pneumonia in newborns. Turk J Pediatr. 2006;48(3):
213220
36. Evans ME, Schaffner W, Federspiel CF, Cotton RB, McKee
KT Jr, Stratton CW. Sensitivity, specicity, and predictive value of

e232 NeoReviews Vol.15 No.6 June 2014

Downloaded from http://neoreviews.aappublications.org/ at Indonesia:AAP Sponsored on November 19, 2014

infectious diseases

body surface cultures in a neonatal intensive care unit. JAMA.

1988;259(2):248252
37. Cordero L, Ayers LW, Davis K. Neonatal airway colonization
with gram-negative bacilli: association with severity of bronchopulmonary dysplasia. Pediatric Infectious Disease Journal. 1997;16(1):1823
38. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH. The
inuence of inadequate antimicrobial treatment of bloodstream
infections on patient outcomes in the ICU setting. Chest. 2000;118
(1):146155
39. Chastre J, Luyt CE, Trouillet JL, Combes A. New diagnostic
and prognostic markers of ventilator-associated pneumonia. Curr
Opin Crit Care. 2006;12(5):446451
40. Kirtland SH, Corley DE, Winterbauer RH, et al. The diagnosis
of ventilator-associated pneumonia: a comparison of histologic,
microbiologic, and clinical criteria. Chest. 1997;112(2):445457
41. Palazzo SJ, Simpson T, Schnapp L. Biomarkers for ventilatorassociated pneumonia: review of the literature. Heart Lung. 2011;
40(4):293298
42. Centers for Disease Control and Prevention (CDC). Guidelines for prevention of healthcare-associated pneumonia. MMWR.
March 26,2004;53(RR03);136
43. American Thoracic Society; Infectious Diseases Society of
America. Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcare-associated pneumonia.
Am J Respir Crit Care Med. 2005;171(4):388416
44. Kollef MH. Prevention of hospital-associated pneumonia and
ventilator-associated pneumonia. Crit Care Med. 2004;32(6):
13961405
45. Resar R, Pronovost P, Haraden C, Simmonds T, Rainey T,
Nolan T. Using a bundle approach to improve ventilator care
processes and reduce ventilator-associated pneumonia. Jt Comm J
Qual Patient Saf. 2005;31(5):243248

ventilator-associated pnuemonia

46. Lorente L, Blot S, Rello J. Evidence on measures for the

prevention of ventilator-associated pneumonia. Eur Respir J. 2007;
30(6):11931207
47. Cordero L, Sananes M, Ayers LW. Comparison of a closed
(Trach Care MAC) with an open endotracheal suction system in
small premature infants. J Perinatol. 2000;20(3):151156
48. Christensen RD, Henry E, Baer VL, et al. A low-sodium
solution for airway care: results of a multicenter trial. Respir Care.
2010;55(12):16801685
49. Craven DE, Goularte TA, Make BJ. Contaminated condensate
in mechanical ventilator circuits: a risk factor for nosocomial
pneumonia? Am Rev Respir Dis. 1984;129(4):625628
50. Torres A, Gatell JM, Aznar E, et al. Re-intubation increases
the risk of nosocomial pneumonia in patients needing mechanical
ventilation. Am J Respir Crit Care Med. 1995;152(1):137141
51. Saiman L, Ludington E, Dawson JD, et al; National Epidemiology of Mycoses Study Group. Risk factors for Candida species
colonization of neonatal intensive care unit patients. Pediatr Infect
Dis J. 2001;20(12):11191124
52. Terrin G, Passariello A, De Curtis M, et al. Ranitidine is
associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics. 2012;129(1):e40e45
53. Herruzo-Cabrera R, Garca Gonzalez JI, Garca-Magan P, del ReyCalero J. Nosocomial infection in a neonatal intensive care unit and its
prevention with selective intestinal decolonization. A multivariant
evaluation of infection reduction. Eur J Epidemiol. 1994;10(5):573580
54. Rojas MA, Lozano JM, Rojas MX, et al. Prophylactic probiotics to prevent death and nosocomial infection in preterm
infants. Pediatrics. 2012;130(5):e1113e1120
55. Sole ML, Poalillo FE, Byers JF, Ludy JE. Bacterial growth in
secretions and on suctioning equipment of orally intubated patients:
a pilot study. Am J Crit Care. 2002;11(2):141149

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NeoReviews Quiz Requirements

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1. A 10-day-old, 28-week-gestational-age male infant who has been on the ventilator has worsening clinical
status and is suspected of having pneumonia. Which of the following statements regarding the development of
ventilator-associated pneumonia (VAP) is correct?
A. Radiographic characteristics of VAP are very distinct and consistent, with a diffuse pattern of consolidation
at onset.
B. A patient needs to be intubated for at least 5 days before onset of infection to have an official diagnosis of
VAP.
C. Opiate treatment for sedation has been associated with increased risk of VAP.
D. A key feature in effective prevention of VAP is frequent suctioning and periodic replacement of the
endotracheal tube.
E. A concurrent bloodstream infection rules out the diagnosis of VAP.
2. In the 10-day-old, 28-week-gestational-age patient, which of the following statements regarding diagnosis
of VAP is correct?
A. It would be considered the standard of care to perform bronchoscopic bronchoalveolar lavage for the
purpose of diagnosis in this patient.
B. The definition of VAP for neonates has been well established since the 1998 criteria published in a joint
effort between the Centers for Disease Control and Prevention and the American Academy of Pediatrics.
C. A sterile tracheal aspirate culture has a high negative predictive value for VAP.
D. Tracheal aspirates have excellent sensitivity (>98%) but poor specificity for diagnosis of VAP.
E. C-reactive protein has been very useful in the diagnosis of VAP, for distinguishing VAP from other disease
processes, and for use in trials for establishing diagnostic criteria.
3. A tracheal aspirate is obtained from the patient who is suspected of having VAP. Which of the following has
been found regarding tracheal aspirates in neonates who have VAP?
A. Gram-positive organisms are the most common bacteria noted in tracheal aspirates.
B. In general, the most common finding from tracheal aspirates of neonates suspected of having VAP are
sterile or have a single-organism growth.
C. Streptococcus gallolyticus is found in 50% of neonates who have VAP.
D. Bronchoalveolar lavage with a blind protected catheter generally results in higher recovery of
polymicrobial infections.
E. Pseudomonas aeruginosa is a pathogen recovered from airway secretions in VAP by using both tracheal
aspirate and bronchoalveolar lavage methods.
4. The clinical care team has determined that the patient has VAP. What are appropriate principles regarding
treatment for VAP in neonates at this gestational age?
A. Clear consensus guidelines for the treatment of very low birthweight infants were published by the Centers
for Disease Control and Prevention (CDC), first in 1999 and updated in 2010.
B. In the majority of cases, if the patients condition is stable, the treatment of VAP is extubation to
continuous positive airway pressure or nasal cannula, and does not require antibiotics.
C. Antibiotics should only be started after a pathogenic organism associated with VAP has been identified.
D. Empiric treatment may include an antipseudomonal agent such as piperacillin/tazobactam.
E. Because organisms causing VAP are generally derived from mouth flora, penicillin is a reasonable first-line
treatment or can be used if treatment is desired when no organism is recovered.

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ventilator-associated pnuemonia

5. Your neonatal intensive care unit (NICU) is developing a bundle for prevention of VAP. Which of the following
components may be a reasonable part of the protocol based on the studies discussed in this article?
A. Neonate should be positioned in the prone position at least one-half of the time if he or she has been
intubated for more than 2 days.
B. Separate suctioning equipment should be used for tracheal and oral secretions.
C. Respiratory circuits should be changed on a routine basis, daily or twice a day.
D. Normal saline has been shown to be the optimal solution for airway suctioning compared with all other
solutions.
E. To minimize gastric aspiration, moderate sedation for vigorously moving infants should be applied,
preferably with opioids.

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Ventilator-Associated Pneumonia in Neonates: An Update

Jeffery S. Garland
Neoreviews 2014;15;e225
DOI: 10.1542/neo.15-6-e225

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