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Differing Pathways of Lower Airway Colonization and Infection According to Mode of Ventilation (Endotracheal vs Tracheotomy)
Pradeep Morar, MD;
Vivian Singh, MD;
Zvoru Makura, MD;
Andrew Jones, MD;
Paul Baines, MD;
Andrew Selby, MD;
Richard Sarginson, MD;
Julie Hughes, RGN;
Rick van Saene, MD
Arch Otolaryngol Head Neck Surg. 2002;128:1061-1066.
ABSTRACT
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Objectives To determine whether the pathogenesis of lower airway colonization and
infection was endogenous (via the oropharynx) or exogenous (via the endotracheal
tube or tracheotomy) during the 2 modes of ventilation in the same subset
of children requiring long-term ventilation.
Design Prospective, observational cohort study.
Setting A pediatric intensive care unit and a respiratory ward.
Patients Consecutive admissions between September 1, 1993, and August 30, 1998.
Measurements and Main Results Cultures were obtained simultaneously from the oropharynx and tracheobronchial
tree on admission to the pediatric intensive care unit, at placement of the
tracheotomy, and afterward twice weekly. Forty-five patients were studied.
Lower airways were always sterile in 6 children, 39 children (87%) developed
a total of 82 episodes of colonization, and 17 (38%) progressed to 25 episodes
of infection. The number of infected children was halved once they had a tracheotomy
(7 children [16%]). Of the 107 episodes of colonization and infection, 41
and 66 occurred during endotracheal ventilation and via a tracheotomy, respectively.
Primary endogenous episodes of colonization and infection due to bacteria
present in the admission flora in the pediatric intensive care unit were significantly
more common with endotracheal ventilation than during ventilation via a tracheotomy
(31/41 [76%] vs 36/66 [55%]; P = .03). Secondary
endogenous and exogenous episodes of colonization and infection due to bacteria
associated with the respiratory ward were significantly more frequent when
ventilation was continued through a tracheotomy than during endotracheal ventilation
(30/66 [45%] vs 10/41 [24%]; P = .02).
Conclusions Surveillance samples allow the distinction between primary endogenous
("imported" bacteria) from secondary endogenous and exogenous ("nosocomial"
microorganisms) colonization and infection. This classification permits the
development of preventive strategies to control both endogenous and exogenous
pathways.
INTRODUCTION
THE OROPHARYNGEAL flora has been compared with the flora of the lower
airways in adult patients requiring ventilation endotracheally and subsequently
via a tracheotomy.1-4
Longitudinal serial samples from the oropharynx and lower airways are required
for that comparison. The 3 studies in adult patients with tracheotomies1-3 showed that the microorganisms
isolated from the lower airways differed from the bacteria carried in the
oropharynx. Bartlett et al1 demonstrated in
16 patients that there was a poor correlation between oropharyngeal and tracheal
cultures. Aerobic gram-negative bacilli (AGNB), mainly Pseudomonas and Serratia species, were the
predominating potential pathogens. Niederman et al2
examined 14 adult patients and found that the flora differed at the 2 sites
and that Pseudomonas species persisted more often
in the tracheal than in the oropharyngeal cultures. Palmer et al3
confirmed in 7 patients that colonization differed between the oropharynx
and trachea. Pseudomonas and Serratia species again emerged as the common potential pathogens. In 14 endotracheally
ventilated patients, Niederman et al4 reported
that Pseudomonas species were found more often in
the tracheobronchial tree than in the oropharynx.
As pediatric studies using the design of obtaining cultures simultaneously
from the oropharynx and tracheobronchial tree were lacking, our group embarked
on a prospective observational cohort study in 45 children requiring long-term
ventilation initially via an endotracheal tube and subsequently via a tracheotomy.
The objective was to unravel the pathway of lower airway infections: whether
the pathogenesis of colonization and infection was endogenous (via the oropharynx)
or exogenous (via the endotracheal tube or tracheotomy) during the 2 different
modes of ventilation (Figure 1).
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The endogenous (solid arrows) and exogenous (gray arrows) routes
of colonization and infection of lower airways. In patients who are endotracheally
ventilated, the endogenous pathway prevails, as opposed to the exogenous route
being substantial once the patient receives a tracheotomy.
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PATIENTS AND METHODS
This prospective observational investigation was undertaken during a
5-year period in the pediatric intensive care unit (PICU) and afterward at
the respiratory ward of the Alder Hey Children's Hospital, Liverpool, England,
during the period from September 1, 1993, through August 30, 1998. Children
requiring mechanical ventilation, initially endotracheally and subsequently
via tracheotomy, were consecutively enrolled into this cohort study of children
with tracheotomies.
PATIENTS
Forty-five patients, 33 boys and 12 girls, were enrolled consecutively
during the 5 years. Median age was 6.4 months, with a range of 0 to 180 months.
The mean age was 42.8 months (SD, 65 months) at the time of admission to the
PICU (Table 1). Twelve of the
children had underlying neurologic disease. This included 7 children with
cerebral palsy, 3 patients with Guillain-Barré syndrome, and 1 patient
each with status epilepticus and central apnea syndrome. Four patients underwent
tracheotomies for purely pulmonary problems. Airway obstruction was the indication
for tracheotomy in 26 patients. Of these, 10 were for upper airway obstructions,
8 for subglottic stenosis, 3 for bilateral vocal cord palsy, 2 for subglottic
hemangiomas, and 1 each for extratracheal compression, laryngeal papilloma,
and tracheomalacia. One patient had a myopathic disorder, requiring a permanent
tracheotomy, and 2 patients had difficulties being weaned off the ventilator
after a spinal operation for the correction of kyphoscoliosis.
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Table 1. Patient Demographics
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TRACHEOTOMY
All tracheotomies were performed electively by means of the routine
methods used in children by most authorities.5
Immediate aftercare, including daily stoma care, suctioning, and change of
tracheotomy tube, were all done under strict protocols of hygiene and sterility.6
END POINTS
There was only 1 intervention: the change of mode of ventilation, initially
endotracheally and subsequently via tracheotomy. The impact of the placement
of a tracheotomy was evaluated by comparing the following factors for both
ventilation modes: (1) the number of children who were colonized with potentially
pathogenic microorganisms (PPMs) in the lower airways; (2) the number of episodes
of colonization; (3) the number of children with infected lower airways; (4)
the number of infection episodes; and (5) the number of episodes of primary
endogenous, secondary endogenous, and exogenous colonization and infection.
SAMPLING
Surveillance samples of the oropharynx were obtained immediately on
admission to the PICU before endotracheal ventilation and before the placement
of the tracheotomy, and twice weekly afterward. The reason for taking these
samples is to detect the carrier state of the potential pathogens that allow
us to distinguish the endogenous from the exogenous pathway.
Diagnostic samples of lower airway secretions were taken once weekly,
and on clinical indication, ie, tracheal aspirates that were turbid.
ANTIBIOTIC POLICY DURING THE STUDY
Systemic antibiotics were given only in case of infection. Infection
was diagnosed on the basis of clinical signs of infection, including temperature
greater than 38.5°C, leukocytosis with a white blood cell count greater
than 12 x 103/µL, and elevated C-reactive protein level
to greater than 15 µg/mL, combined with purulent tracheal aspirates
yielding 106 colony-forming units (CFU)/mL or more.7-8
All requirements had to be fulfilled for the diagnosis of infection. Tracheobronchitis
was distinguished from pneumonia by the absence of chest radiographic changes.
Infection due to gram-positive bacteria was, in general, treated with a first-generation
cephalosporin, while a third-generation cephalosporin was given in children
who developed a lower airway infection caused by AGNB. Infection in general
was treated with a 5-day course of antibiotics, followed by clinical reexamination
of the patient.
DEFINITIONS
The following definitions were used, in accordance with van Saene et
al.9
1. Carriage or the carrier
state existed when the same bacterial strain was isolated from at least
2 consecutive throat samples, in any concentration, during a period of at
least 1 week.
2. Colonization of the lower airways was defined
as the presence of a microorganism in the lower airways; the diagnostic sample
yielded less than 106 CFU/mL of diagnostic sample. The concentration
of leukocytes in the lower airway secretions was, in general, few (+) or moderate
(++), on a semiquantitative scale of +, ++, and +++ (many).
3. Infection of the lower airways was defined
as a microbiologically proved diagnosis of systemic inflammation. The diagnostic
sample obtained from the lower airways yielded greater than or equal to 106 CFU/mL of sample, and there were many leukocytes in the lower airway
secretions.
Tracheobronchitis was defined as follows: (a) purulent endotracheal aspirate (white blood cells +++),
(b) fever (temperature, >38.5°C), (c) leukocytosis (white blood cell count, >12 x 103/µL)
or leukopenia (white blood cell count, <4 x 103/µL),
(d) 106 CFU/mL or more of tracheal aspirate,
and (e) elevated C-reactive protein level of greater
than 15 µg/mL.
Bronchopneumonia was diagnosed by means of
the same 5 criteria as above, combined with the presence of a new or progressive
pulmonary infiltrate on chest radiograph for more than 48 hours.
4. Primary endogenous colonization and infection
was defined as colonization and infection of the lower airways caused by a
PPM isolated from the lower airway secretions, and carried by the patient
in the throat, at the time of admission to the PICU and/or tracheotomy.
5. Secondary endogenous colonization and infection
was defined as colonization and infection of the lower airways caused by a
PPM isolated from the tracheal aspirate, and not carried in the throat at
the time of admission to the PICU and/or tracheotomy, but appearing later.
6. Exogenous colonization and infection was
defined as colonization and infection of the lower airways caused by a PPM
isolated from the tracheal aspirate that was not previously carried by the
child in the throat at any time.
7. Indigenous flora were microorganisms, eg,
viridans streptococci, carried by healthy individuals at high concentrations,
ie, 106 CFU/mL of saliva or more.
8. Community PPMs were PPMs carried by varying
percentages of healthy people, including Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.
9. Hospital PPMs included AGNB such as Klebsiella, Enterobacter, Acinetobacter, Pseudomonas, and Stenotrophomonas species, and methicillin-resistant S aureus. They are abnormal in healthy people and are carried
by individuals with both acute and chronic underlying diseases.
10. Nosocomial microorganisms were microorganisms
that were not present in the patients' admission flora to the PICU, or at
the time of placement of a tracheotomy. Nosocomial microorganisms were PICU
and/or respiratory ward related and caused secondary endogenous and exogenous
colonization and infection of the lower airways.
STATISTICAL ANALYSIS
A statistical package (Arcus QuickStat; StatsDirect Ltd, Ashwell, England)
was used for analysis of the data. The number of children colonized and infected
before and after tracheotomy was analyzed by means of McNemar 2-tailed test
after Liddell. Proportions analysis using a 2-tailed exact method with 95%
confidence intervals was used for the comparison of the percentages of episodes
of both colonization and infection, during the pretracheotomy and posttracheotomy
periods. The same analysis was used to compare the different types of colonization
and infection during the 2 modes of assisted ventilation: primary endogenous,
secondary endogenous, and exogenous. Nosocomial colonization and infection
episodes accounted for only secondary endogenous and exogenous categories.
RESULTS
PATIENTS
The 45 children had assisted ventilation for a median period of 12 days
(95% confidence interval, 7-24 days; range, 0-103 days) in the pretracheotomy
period, via an endotracheal tube, for a total of 916 days. Assisted mechanical
ventilation continued after tracheotomy via a tracheotomy tube for a further
total of 1559 days, with a median of 12 days (95% confidence interval, 2-28
days; range, 1-281 days) (Table 2).
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Table 2. Ventilation Periods for the 2 Forms of Ventilation
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Of the 45 children enrolled, 6 children who required long-term ventilation
had sterile lower airways throughout the study period whether they were ventilated
via an endotracheal route or via a tracheotomy. Of the 39 children (87%) who
developed a total of 82 episodes of colonization, 17 (38%) progressed to a
total of 25 episodes of infection consisting of both tracheobronchitis and
pneumonia. A total of 122 PPMs were involved in the 107 episodes of colonization
and infection in 39 children.
IMPACT OF PLACEMENT OF TRACHEOTOMY
Both the number of children with colonized airways and the number of
episodes of colonization increased significantly after ventilation through
a tracheotomy (Table 3). As the
children recovered once they had received a tracheotomy, the rate of infected
patients as well as the number of infection episodes decreased. However, these
differences were not statistically significant. Table 4 shows the impact of the mode of ventilation on the 3 types
of lower airway colonization and infection.
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Table 3. Impact of Mode of Ventilation on the Number of Colonized/Infected
Children and on the Number of Episodes of Colonization and Infection*
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Table 4. Impact of Mode of Ventilation on the 3 Pathways Causing Lower
Airway Colonization/Infection*
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Primary endogenous episodes of colonization and infection of the lower
airways were significantly more common when patients were endotracheally ventilated
compared with tracheotomy (31/41 [76%] vs 36/66 [55%]; P = .03). In other words, microorganisms carried in the oropharynx
at the time of endotracheal admission to the PICU caused three fourths of
all episodes during endotracheal ventilation, while half of all episodes that
developed after placement of tracheotomy were due to throat bacteria present
at the time of tracheotomy.
Ward-related bacteria were responsible for 45% (30/66) of all episodes
of colonization and infection once ventilation was continued through a tracheotomy
on the respiratory ward. In contrast, 24% (10/41) of all episodes were due
to bacteria associated with the PICU during ventilation. This difference was
significant at a level of P = .02.
MICROORGANISMS INVOLVED IN COLONIZATION AND INFECTION EPISODES
A total of 81 microorganisms were isolated from the lower airway secretions
of children during 67 episodes of primary endogenous colonization and infection.
Community PPMs, including S pneumoniae, H influenzae, Moraxella catarrhalis, and S aureus, and AGNB (mainly Pseudomonas
aeruginosa) were equally distributed among the endotracheal ventilation
episodes and the episodes incurred during ventilation via a tracheotomy (Table 5). There were a total of 40 episodes
of secondary endogenous and exogenous colonization and infection, yielding
42 microorganisms. There were 10 episodes of secondary endogenous and exogenous
development caused by 2 community bacteria (S aureus
in both) and 8 AGNB (P aeruginosa in 5) during endotracheal
ventilation. After the placement of a tracheotomy, 30 episodes of secondary
endogenous and exogenous pathogenesis developed and were caused by 16 "community"
bacteria (S aureus in 15), 14 AGNB (P aeruginosa in 7), and 2 methicillin-resistant S aureus.
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Table 5. Microorganisms Causing Colonization/Infection*
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COMMENT
Changing the mode of ventilation from endotracheal to a tracheotomy
resulted in most children (87%) being colonized with bacteria in their lower
airways. However, the number of infected children was halved once they had
a tracheotomy (16%). Half of all episodes of colonization and infection during
ventilation via a tracheotomy were caused by microorganisms carried in the
throat at placement of the tracheotomy; the other half were due to bacteria
acquired on the respiratory ward. This contrasts with the microbial distribution
during endotracheal ventilation: 25% PICU acquired and 75% of episodes due
to bacteria present in the admission flora.
Apparently, keeping the lower airways sterile in a child with a tracheotomy
is impossible. The wound created by the tracheotomy represents an anatomic
aberration. The presence of a plastic device always causes a low grade of
mucocutaneous inflammation. The pH of the lower airway secretions is increased
and the normal position of the trachea is altered. A tracheotomy bypasses
the physiologic filter system limiting bacterial invasion into the lower airways.
In the presence of microbial exposure, microorganisms show an affinity for
the tracheotomy rather than the oropharynx as the site of acquisition. In
addition, introduction of microorganisms directly into the lower airways via
the tracheotomy as a result of repeated suctioning and manipulation of the
trachea represents an important exogenous pathway. However, only 16% of the
children with a tracheotomy had an infection, mainly because of a substantial
improvement of their underlying medical condition. The infection rate was
30% when they required intensive care including endotracheal ventilation.
Most children left the PICU for the respiratory ward once they had a
tracheotomy. Half of all colonization and infection episodes were due to bacteria
that the patients did not carry in their throats but acquired on the respiratory
unit, mainly via the tracheotomy, ie, exogenous pathway. In contrast, 75%
of all episodes that developed during endotracheal ventilation were caused
by bacteria not related to the PICU but present in the oropharyngeal admission
flora.
We believe that the criterion of the oropharyngeal carrier state allowed
us to unravel the different routes of colonization and infection due to the
change of mode of ventilation. The traditional time cutoff of 48 hours used
in the 4 adult studies1-4
failed to distinguish the 3 forms of colonization and infection of the lower
airways. The distinction between primary endogenous colonization and infection
due to bacteria not related to the PICU and respiratory ward from secondary
endogenous and exogenous colonization and infection caused by PICU and respiratory
ward bacteria has proved to be helpful in unraveling the impact of the change
of mode of ventilation.
Attempts to control colonization and infection of the lower airways
in patients with a tracheotomy date from the epidemic of poliomyelitis in
1952.10 Lepper et al10
used aerosols of polymyxin B sulfate in 72 patients to prevent colonization
and infection by P aeruginosa. While P aeruginosa was effectively controlled, the polymyxin aerosols failed
in controlling S aureus and Proteus species intrinsically resistant to the polymyxins. Fifty years later,
Palmer et al11 evaluated the efficacy of aerosolized
aminoglycosides, gentamicin sulfate and amikacin sulfate, delivered via a
nebulizer to the lower airways of 6 patients. The investigators reported the
eradication of Pseudomonas species, Serratia marcescens, and Enterobacter aerogenes.
In the 1970s, Klastersky et al12 instilled,
intratracheally, aminoglycosides alone and in combination with polymyxin B
in neurosurgical patients with tracheotomies. In the first study, 85 patients
were randomized to receive either endotracheal gentamicin or isotonic sodium
chloride solution.12 Both colonization and
infection due to AGNB were significantly reduced. The second study in 45 patients
compared gentamicin vs paromomycin sulfate plus polymyxin B.13
Again, colonization and infection caused by AGNB were effectively controlled.
Although the endotracheal administration of gentamicin was better tolerated
than the combination, emergence of resistant AGNB was a more serious problem
in the patients receiving monotherapy compared with the combination.
The methods of aerosolization and endotracheal instillation do not take
into account the pathways of colonization and infection. There is consensus
that microorganisms carried in the oropharynx migrate into the lower airways,
ie, the endogenous route. We found that in children with tracheotomy the exogenous
route, ie, microorganisms immediately introduced into the lower airways and
bypassing the oropharynx, substantially contributed to the colonization and
infection of the lower airways in patients with tracheotomies. Our 5-year
study using longitudinal serial sampling of both the oropharynx and lower
airways enabled us to distinguish the endogenous route from the exogenous
route. In addition, in comparing the oropharyngeal flora on admission to the
PICU and at the time of placement of a tracheotomy, primary carriage was distinguished
from secondary carriage, ie, the oropharyngeal carrier state of microorganisms
acquired during the stay on the PICU and respiratory ward.
This study using carriage for classifying colonization and infection
in children with tracheotomies shows that about half the population acquired
nosocomial, ie, respiratory ward–associated, microorganisms. The most
recent meta-analysis of selective decontamination of the digestive tract in
patients receiving mechanical ventilation shows that 0.5 g of a 2% paste of
polymyxin B sulfate and tobramycin sulfate applied in the lower part of the
cheeks 4 times a day was effective in eradicating microorganisms already present
and in preventing secondary endogenous colonization and infection.14 Hygiene is indispensable for the control of exogenous
colonization and infection. However, in our experience, keeping high standards
of hygiene in children with, for example, cerebral palsy is not always possible,
as 87% of the study population acquired microorganisms in the lower airways.
The topical application of the same mixture on the tracheotomy site has been
shown to be a promising method in the control of exogenous colonization and
infection.15 A randomized trial evaluating
topical paste applied both in the oropharynx and on the tracheotomy site compared
with placebo is under way.
AUTHOR INFORMATION
Accepted for publication February 13, 2002.
Corresponding author and reprints: Pradeep Morar, MD, 21a Tanhouse
Ln, Parbold WN8 7HG, Lancashire, England (e-mail: paddy{at}morarp.freeserve.co.uk).
From the Departments of Otorhinolaryngology (Drs Morar, Singh, Makura,
and Jones), Paediatric Intensive Care (Drs Baines, Selby, and Sarginson),
and Clinical Microbiology and Infection Control (Ms Hughes and Dr van Saene),
Royal Liverpool Children's NHS Trust of Alder Hey, Liverpool, England.
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