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Bacterial Colonization of Endotracheal Tubes in Intubated Neonates
David R. Friedland, MD, PhD;
Michael A. Rothschild, MD;
Mercedes Delgado, MD;
Henry Isenberg, PhD;
Ian Holzman, MD
Arch Otolaryngol Head Neck Surg. 2001;127:525-528.
ABSTRACT
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Objective To obtain in vivo bacterial colonization profiles on endotracheal tubes
at different sites in the neonatal airway in an attempt to better characterize
one potential element of chondritis.
Design A case series in which cultures were obtained from calculated segments
of 33 endotracheal tubes immediately following extubation. This allowed for
sampling at specific levels of the airway corresponding to the trachea, the
subglottis, and the oropharynx. Data collected included gender, race, duration
of intubation, use of antibiotic therapy, comorbidities, gestational age at
birth and extubation, crown-rump length, weight, radiographic distance from
tube tip to carina, and culture results.
Setting Newborn intensive care unit at a tertiary care medical center.
Patients Twenty-nine neonates intubated for longer than 24 hours (range, 24 hours
to 15 days).
Main Outcome Measures Bacterial and fungal cultures obtained from 3 endotracheal tube segments
for each extubation.
Results A statistically significant difference (P<.05)
was found in colonization rates between patients intubated for less than 4
days and those intubated for longer periods. No significant difference was
noted in bacterial profile between the 3 sites.
Conclusions Data demonstrate that bacterial colonization of an indwelling object
in the neonatal airway increases with the duration of intubation. Furthermore,
4 days seems to represent a critical period in the formation of such colonization
(possibly in the form of a biofilm). These bacteria may contribute to the
chondritis known to precede the development of subglottic stenosis. Further
studies are indicated to suggest ways to interrupt this process and reduce
the incidence of airway injury.
INTRODUCTION
LONG-TERM intubation and ventilatory support for neonates with respiratory
distress syndrome was first introduced 3 decades ago1
and has since resulted in the salvage of innumerable premature infants. Prolonged
endotracheal intubation, however, can result in the development of clinically
significant subglottic stenosis in up to 12% of the patients.2, 3, 4
This has resulted in a new group of patients who are tracheotomy dependent
in early childhood. Adequate surgical treatment of such patients is difficult
and attention has focused on the prevention of subglottic stenosis when long-term
intubation is indicated.
Much attention has focused on the endotracheal tube itself. Minimization
of trauma from intubation and suctioning has been advocated to limit airway
injury. Furthermore, in adults and older children, benefits have been claimed
for the use of high-volume low-pressure cuffs, as well as frequent cuff pressure
monitoring and soft cuffs at the larynx.3, 5, 6
The size of the endotracheal tube relative to the airway lumen has been examined,
and recommendations have been made to avoid an excessively tight fit in the
subglottis.7, 8 In an effort to
minimize friction trauma by tube motion, nasotracheal intubation has been
supported and tube fixation devices have also been devised.9
Attention has alternatively turned to the underlying cause of subglottic
stenosis. The first step in the development of subglottic stenosis is mucosal
ischemia induced by cuff or tube pressure. This can occur within hours of
intubation and in neonates predominates in the posterior subglottis where
endotracheal tube contact with the trachea would be maximal.10
A stepwise process ensues in which mucosal ischemia leads to ulceration and
the exposure of underlying cartilage. Exposed cartilage is then susceptible
to infection and resultant chondritis with scarring and stenosis on healing.
While many of the measures described above focus on reducing mucosal ischemia,
few studies have examined the later stages of tissue damage. In particular,
the role of potential pathogens in causing or aggravating laryngotracheal
chondritis has not been adequately investigated.
No organisms have been identified as unique to the subglottis or as
being particularly virulent in exploiting mucosal damage. Several studies
to date have attempted to characterize the bacteriologic profile of the subglottis;
however, access to the region is difficult. Most studies have examined the
bacterial profile at the time of surgery by sampling tissue directly through
a tracheotomy site or bronchoscope.11, 12
That these patients require surgery indicates a more serious condition and
may bias results toward patients who have already suffered airway injury.
Our study focuses on the endotracheal tube itself and attempts to characterize
those organisms that may opportunistically colonize such an indwelling device.
This article demonstrates a time-dependent bacterial colonization of endotracheal
tubes in intubated neonates and examines whether the subglottic region is
unique. Such information may help us to better understand potential pathogens
in the formation of neonatal subglottic stenosis.
PATIENTS AND METHODS
PATIENTS
All newborns orally intubated longer than 24 hours in the neonatal intensive
care unit were eligible for inclusion in this study. Neonates undergoing previous
airway surgery or in whom the endotracheal tube could not be immediately processed
were excluded. This study examined the endotracheal tubes from 29 neonates
representing 33 extubations. The duration of intubation ranged from 24 hours
to 15 days (mean, 5.4 days; median, 4 days). Information collected about the
neonates included gestational age at birth, birth weight, duration of intubation,
age at extubation, antibiotic therapy, previous positive culture results,
crown-rump and crown-heel length, weight at extubation, and distance of endotracheal
tube tip to carina on last chest radiograph. Admission criteria were available
for 26 neonates and include 3 with clinical sepsis, 5 for rule-out sepsis,
and 6 who underwent corrective cardiac surgery.
CALCULATION OF CORRESPONDING AIRWAY SITES
The goal of this study was to compare bacterial profiles at the distal
trachea, subglottis, and pharynx. As such a method was devised to determine
the site on the endotracheal tube corresponding to these regions. The distal
trachea was taken as the terminal 1 cm on the endotracheal tube if the last
chest radiograph demonstrated normal tube position. The position of the subglottis
and pharynx required calculation of trachea length and relative positioning
of the endotracheal tube.
The length of each neonate's trachea was calculated based on the normogram
devised by Rotschild et al.13 The length of
the trachea (L) was determined by correlation with the crown-rump length measured
in centimeters (CRL):
The last chest radiograph for each neonate was examined and the distance
from the tip of the endotracheal tube to the carina was measured. This distance
(C) was not corrected for radiographic magnification as examination demonstrated
negligible magnification in this setting. The distance from endotracheal tube
tip to the subglottis (S) was then determined by the following formula:
The factor of 0.3 cm was added to ensure that the sampled section was
not above the level of the vocal folds. The pharynx was then calculated as
3 cm proximal to the subglottis.
COLLECTION OF ENDOTRACHEAL TUBES
A sterile work area was prepared next to each infant at the time of
extubation. Included on the field were a ruler, scissors, and culture tubes.
Formula 2 was used to calculate the subglottis and pharynx; these points were
marked on the sterile ruler. A 1-cm segment of the endotracheal tube corresponding
to the oropharynx, subglottis, and distal trachea were cut under sterile conditions
immediately on extubation. Specimens were sent to the microbiology laboratory,
where gram, Giemsa, and acid-fast bacillus staining was performed. In addition,
bacterial, fungal, and acid-fast bacillus cultures were obtained.
RESULTS
There were 33 extubations from 29 neonates. Culture results for each
site were obtained in most cases: endotracheal tube tip (n = 32), subglottis
(n = 33), and pharynx (n = 31). Positive cultures yielded the identification
of an organism while negative cultures yielded no growth after 5 days' incubation.
Approximately 50% of samples demonstrated growth. No statistically significant
difference was noted in the culture rate between sites (Table 1). A variety of organisms were cultured but there was a proponderance
of Staphyloccocus epidermidis (Table 2). No significant difference was noted between sites with
regard to the organism cultured.
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Table 1. Incidence of Cultures With Positive Yields From Endotracheal
Tube (ETT) Section by Site
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Table 2. Organisms Identified on Endotracheal Tube (ETT) Culture by
Site
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Results from the subglottis were compared with the pharynx and the distal
trachea to determine if there was a unique microbial profile in this region
(Table 3). In general, a positive
culture result in the subglottis indicated a positive culture result at the
other sites. Although not statistically significant, culture results in the
subglottis more closely correlated with the distal trachea than with the pharynx.
For example, in only one instance was the subglottic culture negative for
organisms but in another site was positive; this was in the pharynx. Further,
a different organism was found at another site only 3 times; 2 of these cases
were in the pharynx.
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Table 3. Relationship of Subglottic Culture Results to Other Sites*
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The incidence of multiple organisms was similarly low. On one occasion
each, cultures from the subglottis and pharynx grew 2 organisms. No cultures
or stains were positive for Giemsa or acid-fast bacilli. In 2 instances Candida species was identified on culture but not potassium
hydroxide preparation and thus was considered a laboratory contaminant. In
these 2 cases the clinical course also did not correlate with a fungal infection.
For those patients whose information was complete regarding the use
of antibiotic agents (n = 22), culture results were analyzed. In the 12 cases
in which antibiotic agents were administered, culture results were evenly
divided between positive for organisms (n = 6) and no growth (n = 6). In the
10 cases in which no antibiotic agent was administered, the culture results
were 8 positive for organisms and 2 no growth. All cases were treated with
ampicillin sodium and/or gentamicin sulfate. Preantibiotic blood cultures
that were positive for organisms demonstrated no significant correlation with
the incidence of a positive culture of the identity of the organism. A  2 analysis of the use of antibiotic agents and the incidence of negative
culture results was not statistically significant.
The incidence of a positive culture after 4 days of intubation was statistically
significant by 2 analysis (P<.025, 2 test). Only 39% of the cultures were positive if the neonate was intubated
for 4 days or less (7 of 18 cases). Intubations of longer than 4 days resulted
in an 80% positive culture rate (12 of 15 cases).
COMMENT
This study did not demonstrate any unique microorganism on endotracheal
tubes in the neonatal subglottis. Rather, a variety of organisms were identified
inhabiting most regions of the respiratory tract. This agrees with other studies'
sampling the airway itself in which polymicrobial flora has been demonstrated.
In a study of swab cultures of the subglottis during bronchoscopy, Brown and
Manning12 found 19 different organisms. Similarly,
Brown and Montgomery11 found a variety of organisms
in tracheal granulation tissue at T-tube sites. Our study found Staphylococcous species as the most prevalent organisms, agreeing with
the findings of Brown and Montgomery. Brown and Manning12
in contrast demonstrated a preponderance of normal flora followed by Staphylococcus aureus. Both prior investigations also demonstrated
a high incidence of Pseudomonas species, which was
demonstrated on the endotracheal tube in only one instance.
An examination of the flora in individual cases reveals a sharp contrast
between the present study and those previously reported. Our investigation
found a low incidence of polymicrobial flora in each case, whereas Brown and
Montgomery11 and Brown and Manning12 found, on average, more than 2 isolates per patient.
This may indicate that endotracheal tube colonization is exclusive for a single,
and perhaps more virulent, organism. In contrast, the trachea may enable habitation
by many species simultaneously.
Culture results from the endotracheal tubes in this study may, in part,
represent luminal bacteria as well. If this were the preponderant source of
culture results, one would expect higher rates of positive culture results
at the open end (ie, distal tip) where bacteria would enter. As listed in Table 3, no such stratification of culture
results was found. Nevertheless, the study method has since been modified
to remove the luminal surface from culture preparations.
The use of antibiotic therapy in preventing the sequelae of infected
or inflamed cartilage is intuitively rational but not supported by these data.
Sasaki et al,14 in a canine model, found bacterial
levels in the larynx to be reduced by the administration of perioperative
antibiotic agents and posttracheotomy wound care. From this they inferred
that reducing bacterial counts would reduce the duration of an inflammatory
response and, thus, promote better healing. Supance15
tested this paradigm, also in a canine model. He intubated 2 groups of dogs
for 14 days with 1 group receiving steroids and antibiotic agents. On postextubation
analysis of a cross-sectional area and microscopic examination of tissue,
no significant difference was found between the 2 canine groups. He concluded
that antibiotic agents lacked efficacy in preventing subglottic stenosis in
the canine model.
Our study, although using a different outcome measure, similarly found
that antibiotic agents play a small role in influencing potential predisposing
factors for stenosis in the subglottis. That is, colonization of the indwelling
endotracheal tube was unaffected by systemic antibiotic therapy. Furthermore,
Brown and Manning12 also found no correlation
between the results of swab cultures of the subglottis and the use of antibiotic
agents. They did, however, recommend empiric penicillin as it has few adverse
effects and may help reduce inflammation. Brown and Montgomery11
likewise recommended antibiotic therapy based on anecdotal evidence of reduction
in tracheal granulation tissue with T tubes.
Intubation for longer than 4 days did demonstrate statistical significance
for obtaining positive bacterial culture results. This time-dependent colonization
was also observed by Brown and Manning.12 They
found 10 days to be significant in the development of pathogenic cultures.
In their study, neonates intubated for shorter periods generally demonstrated
only normal flora. In an effort to explain these results, one must consider
the theory of biofilm formation. Biofilms form on implanted materials and
consist of an adherent matrix of bacteria. These matrices are resistant to
antibiotic agents and host responses, in contrast to simple colonies of bacteria.16 In a study by Malaisrie et al,17
the formation of biofilms on facial plastic implants was studied. They found
that incubation of the material with bacteria for 7 days was universally sufficient
for the formation of a biofilm.
Scanning electron microscopy would be necessary to confirm that the
bacteria cultured in this study were in the form of a biofilm on the endotracheal
tube. This arm of our study has recently begun, but the microscopy data are
yet incomplete. This investigation found single organisms that, if in a biofilm
matrix, would exclude and prevent other organisms from occupying the same
region of the indwelling catheter. Further, antibiotic therapy had no affect
on the rate of colonization of the endotracheal tube, possibly owing to resistance
imparted by a biofilm.
The formation of a biofilm on the endotracheal tube could provide for
a resistant colony of bacteria in the neonatal airway. Such bacteria may promote
an inflammatory response in the narrow subglottis leading to scarring and
the development of subglottic stenosis. Further investigation into biofilm-resistant
materials and biofilm-preventing medications or chemicals needs to be pursued.
Although frequent endotracheal tube changes may help to prevent the formation
of a biofilm, the trauma and risk imposed by such changes are thought to outweigh
the benefits. Further, the role of endotracheal tube bacterial colonization
in the development of subglottic stenosis remains unproven at present.
AUTHOR INFORMATION
Accepted for publication February 21, 2001.
From the Department of Otolaryngology, Johns Hopkins University, Baltimore,
Md (Dr Friedland); and the Departments of Otolaryngology (Dr Rothschild),
Pediatrics (Drs Rothschild, Delgado, and Holzman), and Microbiology (Dr Isenberg),
Mount Sinai School of Medicine, New York, NY. Dr Isenberg is now with the
Department of Pathology, Long Island Jewish Hospital, New Hyde Park, NY.
Reprints: Michael A. Rothschild, MD, Department of Otolaryngology,
Box 1189, Mount Sinai School of Medicine, Fifth Avenue and 100th Street, New
York, NY 10029-6574 (e-mail: doctormike{at}kids-ent.com).
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