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(Chest. 2000;117:513-518.)
© 2000 American College of Chest Physicians

Topical Antibiotics on Tracheostoma Prevents Exogenous Colonization and Infection of Lower Airways in Children*

Pradeep Morar, MD; Zvoru Makura, MD; Andrew Jones, MD; Paul Baines, MD; Andrew Selby, MD; Julie Hughes, RGN and Rick van Saene, MD

* From the Departments of Otolaryngology (Drs. Morar, Makura, and Jones), Paediatric Intensive Care (Drs. Baines and Selby), and Clinical Microbiology/Infection Control (Dr. van Saene and Ms. Hughes), Royal Liverpool Children’s NHS Trust of Alder Hey, Liverpool, UK.

Correspondence to: Dr. Pradeep Morar, 5 Teal Close, Aughton, Lancashire, L39 5QQ; e-mail: paddy{at}morarp.freeserve.co.uk


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Introduction: Patients requiring long-term ventilation are at high risk of lower airway infections, generally of endogenous development. Patients on long-term ventilation, in particular via a tracheostomy, may develop tracheobronchitis or pneumonia of exogenous pathogenesis, ie, caused by microorganisms not carried in the oropharynx. The frequency of exogenous colonization or infection has previously been reported to be as high as 33%. A prospective observational cohort study of 2 years was undertaken to evaluate the efficacy of topical antibiotics in the prevention of exogenous colonization or infection of the lower airways. The antibiotic combination of polymyxin E and tobramycin in a 2% paste was applied four times a day on the tracheostoma.

Materials and methods: A total of 23 children (median age, 4.1 months; range, 0 to 215 months) were enrolled in the study from September 1, 1996, until August 30, 1998. Surveillance samples of the oropharynx were obtained before tracheostomy and thereafter twice weekly. Diagnostic samples of the lower airways were taken once weekly and on clinical indication.

Results: Fourteen children (61%) had a total of 16 episodes of tracheal colonization or infection with 20 potentially pathogenic microorganisms. Only one child had tracheobronchitis with Streptococcus pneumoniae and Haemophilus influenzae during the 2-year study. Of the 16 colonization episodes, 12 (75%) were of primary endogenous pathogenesis, ie, caused by microorganisms present in the oropharynx at the time of tracheostomy. Community microorganisms including S pneumoniae, H influenzae, Moraxella (Branhamella) catarrhalis, and Staphylococcus aureus were the predominating bacteria. Three patients acquired nosocomial bacteria Pseudomonas aeruginosa and Hafnia alvei in the oropharynx, subsequently followed by secondary colonization of the lower airways. There was one failure of the prophylaxis: one patient (4%) had exogenous colonization with Pseudomonas pickettii.

Conclusion: Topical antibiotics applied to the tracheostoma were found to be effective in reducing the exogenous route of colonization of the lower respiratory tract, compared with clinical experience and the literature. This promising technique requires further evaluation in randomized trials.

Key Words: antibiotics • children • colonization • infection • pathogenesis • prevention • tracheotomy


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Patients who are unable to breathe spontaneously and therefore require ventilation are, in general, seriously ill and, therefore, immunocompromised. There is a general consensus that patients requiring long-term ventilation are at high risk of lower airway infections.1 Exogenous lower airway infections are distinguished from endogenous tracheobronchitis and pneumonia.2 The seriously ill patient almost certainly develops a lower airway infection with a potentially pathogenic microorganism (PPM) carried in the oropharyngeal flora at the time when the systemic immunosuppression is at the lowest level, ie, the endogenous pathogenesis of infection. Surveillance samples of the oropharynx and diagnostic samples of the lower airways yield the same PPM in infections of endogenous development. However, patients requiring long-term ventilation, in particular via a tracheostomy, may develop tracheobronchitis or pneumonia of exogenous pathogenesis. Surveillance samples from the throat are negative for the PPM that are isolated from the diagnostic samples of the lower airway secretions. PPM causing exogenous tracheobronchitis or pneumonia almost always include typical "hospital" bacteria such as Pseudomonas, Serratia, and Acinetobacter spp and methicillin-resistant Staphylococcus aureus (MRSA).3 The external sources may be both inanimate and animate reservoirs. Ventilation equipment, nebulizers, and humidifiers have been implicated in exogenous infections,4 whereas other long-stay patients are in general the animate source of PPM responsible for infections of exogenous pathogenesis.5 The exogenous problem has been evaluated in one pediatric study, as far as we are aware.6 The frequency of exogenous colonization or infection was found to be as high as 33%.

A prospective interventional cohort study of 2 years was undertaken to evaluate the efficacy of topical antibiotics applied on the tracheostoma in the prevention of exogenous colonization or infection of the lower airways. The antibiotic combination, composed of polymyxin E and tobramycin in a 2% paste, was applied qid on the tracheostoma for a period of 2 weeks.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
This study was undertaken during a 2-year period as a prospective interventional cohort study, from September 1, 1996, until August 30, 1998. Children requiring long-term mechanical ventilation, initially transtracheally and then via tracheostomy in the pediatric ICU (PICU), were consecutively enrolled in the trial.

Patients
Twenty-three patients, 16 male and 7 female, were enrolled in the study. Median age was 4.07 months (range, 0.03 days to 217 months), and the mean age was 37.8 months (SD = 64.3 months) at the time of the tracheostomy (Table 1 ). Seventeen of the patients had a tracheostomy for airway obstruction. This included six supralaryngeal obstructions, five subglottic stenosis, two subglottic hemangiomata, two vocal cord palsies, one laryngeal papillomata, and one tracheomalacia. In none of these was the tracheostomy regarded as being permanent. Four of the patients had neurologic underlying disease, including two children with cerebral palsy and two with Guillain-Barré syndrome. The former two patients were regarded as having permanent tracheostomies. Only one patient had a tracheostomy performed for a primary respiratory problem, namely bronchopulmonary dysplasia. Finally, one patient had a tracheostomy performed as a precaution before a surgical correction of a kyphoscoliosis.


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  		Table 1.. Patient Demographics

 
Study Intervention
To prevent the immediate transfer of PPM from the external source into the lower airways via the tracheotomy, 0.5 g of paste containing 2% polymyxin E and tobramycin was applied topically to the tracheostomy site four times daily. The paste was applied for a fortnight to cover the postoperative period during which the patient is known to be at high risk of colonization or infection of the lower airways and tracheostomy site.

Sampling
Surveillance Samples: Surveillance samples of the oropharynx were obtained immediately before the placement of the tracheotomy, and twice weekly afterward during the application of the 2% paste with polymyxin E and tobramycin in the PICU. 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: Diagnostic samples of lower airway secretions and tracheotomy site were taken once weekly and on clinical indication. In addition, tracheal aspirates and tracheotomy site exudates that were turbid were obtained in the study.

Microbiological Methods2
Surveillance Samples: Throat swabs were processed qualitatively and semiquantitatively using three solid media, ie, MacConkey, staphylococcal, and yeast agar, and enrichment broth to detect both overgrowth and low-grade carriage.

Diagnostic Samples: Endotracheal aspirates and pus from the tracheostomy site were processed in a qualitative and quantitative way using standard microbiological methods.

For all types of samples, macroscopically distinct colonies were isolated in pure culture. Standard methods for identification, typing, and sensitivity patterns were used for all microorganisms.

Tracheotomy
All tracheotomies were performed electively with the routine methods used by most authorities in children.7 Immediate aftercare, including daily stoma care, suctioning, and change of tracheotomy tube were all conducted under strict protocols of hygiene and sterility.8

Antibiotic Policy During the Study
Systemic antibiotics were given only in case of infection. Infection was diagnosed on clinical signs of infection including fever of 38.5°C, leukocytosis > 12,000 x 109/L, and elevated C-reactive protein (CRP) > 15 µg/mL, combined with purulent tracheal aspirates yielding >= 106 cfu/mL.3 6 All five requirements had to be fulfilled for the diagnosis of infection. Tracheobronchitis was distinguished from pneumonia by the absence of chest radiographic changes. Infection caused by aerobic Gram-positive bacteria was, in general, treated with a first-generation cephalosporin, whereas a third-generation cephalosporin was given in children who developed a lower airway infection caused by aerobic Gram-negative bacilli. Infection in general was treated with a 5-day course of antibiotics, followed by clinical reevaluation of the patient.

Definitions6
Carriage or the carrier state existed when the same bacterial strain was isolated from at least two consecutive throat samples, in any concentration, during a period of at least 1 week.

Colonization of the lower airways was defined as the presence of a microorganism in the lower airways; the diagnostic sample yielded < 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).

Infection of the lower airways was defined as a microbiologically proven diagnosis of systemic inflammation. The diagnostic sample obtained from the lower airways yielded >= 106 cfu/mL of sample, and there were many leukocytes in the lower airway secretions.

Tracheobronchitis was defined as follows:

  1. Purulent endotracheal aspirate (WBC, +++).
  2. Fever > 38.5°C.
  3. Leukocytosis (WBC > 12,000 x 109/L) or leukopenia (WBC < 4,000 x 109/L).
  4. >= 106 cfu/mL of tracheal aspirate.
  5. Elevated CRP > 15 µg/mL.

Bronchopneumonia was defined as the same five criteria as above, combined with the presence of a new or progressive pulmonary infiltrate on chest radiograph for > 48 h.

Primary endogenous colonization or infection was defined as colonization or 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 or tracheotomy.

Secondary endogenous colonization or infection was defined as colonization or 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 or tracheotomy, but appearing later.

Exogenous colonization or infection was defined as colonization or infection of the lower airways caused by a PPM isolated from the tracheal aspirate and not previously carried by the child in the throat at any time.

End points of the study evaluated during the 2 weeks of the intervention were as follows:

  1. Percentage of patients colonized or infected.
  2. Percentage of types of colonization or infection episodes.
  3. Effect of topical antibiotics on the exogenous route.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
All children required mechanical ventilation after the tracheostomy. They were ventilated for a total of 671 days; the median was 2 days (range, 1 to 281 days, 95% confidence interval, 2 to 17), and the mean was 29.2 days (SD = 64.5 days).

Of the 23 children enrolled in the study, 14 (61%) developed colonization or infection of the lower airways during the 2 weeks of topical antibiotics. There were a total of 16 episodes of colonization or infection during the 2-week observation period. Only one child (4%) had tracheobronchitis. Figure 1 shows the distribution of the three types of lower airway colonization: 12 episodes in 11 patients were of primary endogenous pathogenesis; three episodes in three patients were of secondary endogenous pathogenesis, and one patient had one episode of exogenous colonization. Table 2 shows the microorganisms causing the three types of colonization or infection. There was only one infection of primary endogenous development, ie, a tracheobronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae (Fig 2 ) and one failure of the topical prophylaxis, ie, exogenous colonization by Pseudomonas pickettii (Fig 3 ). This bacterium was sensitive to polymyxin E, but resistant to tobramycin in a concentration of 4 mg/L.



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  		Figure 1.. Classification of the 16 colonization or infection episodes in 14 children according to route of acquisition. PE = primary endogenous; SE = secondary endogenous; EX = exogenous.

 

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  		Table 2.. Microbial Distribution Among Colonization/Infection Episodes*

 


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  		Figure 2.. Chart displaying type and semiquantitative growth densities of the microorganisms at the three sites being routinely monitored to determine route of acquisition in child "A" during the study. Endogenous colonization is always preceded by oropharyngeal carriage. If the bacteria are present, eg, S pneumoniae, H influenzae, or Moraxella catarrhalis, before the tracheotomy, that pathway is primary endogenous. In case the bacterium is acquired in the oropharynx after placement of the tracheotomy, the colonization or infection of lower airway is termed secondary endogenous, eg, Enterobacter cloacae.

 


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  		Figure 3.. Chart displaying type and semiquantitative growth densities of the microorganisms at the three sites being routinely monitored to determine route of acquisition in child "B" during the study. Exogenous pathway of colonization caused by P pickettii is shown. It was only present in the lower airway, without previous carriage in the oropharynx. This child also had primary endogenous colonization with Hafnia alvei.

 
After discontinuation of the study maneuver, an additional four children in whom the lower airways were sterile during the paste application each developed one episode of colonization (one exogenous episode caused by S aureus and three secondary endogenous colonization episodes with S aureus (2) and Enterobacter cloacae together with Candida albicans). Moreover, two children who had previous lower airway colonization during the topical paste developed a further three episodes: one primary endogenous episode caused by Pseudomonas aeruginosa, one secondary endogenous caused by Stenotrophomonas maltophilia, and one exogenous episode with S aureus. Overall, 78% of the children had 23 episodes of colonization or infection. A total of five children kept their lower airways sterile.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This 2-year pilot study in 23 children with tracheostomy showed that the topical application of nonabsorbable antibiotics polymyxin E and tobramycin prevented exogenous colonization or infection of the lower airways in all but one patient during the 2 weeks of the intervention after the placement of the tracheostomy. Our previous historical baseline study 6 in 22 children showed six exogenous colonizations or infections in the 2 weeks after the placement of the tracheostomy.

The literature shows that it is virtually impossible to keep the lower airway sterile in that particular subset of children who require long-term tracheostomy.10 Most of these children who need a tracheostomy suffer severe underlying disabilities, eg, cerebral palsy or neurologic impairment. It is well known that the standard of hygiene is difficult to maintain in this population. Breaches of hygiene are responsible for the exogenous pathway of colonization or infection of the lower airways, ie, microorganisms are directly transferred from external sources via the tracheostomy or tube into the lower airway. Several factors contribute to the exogenous development of lower airway colonization or infection. These include the stoma, the tracheostomy tube, ventilation tubing, the low-grade inflammation or ulceration of the stomal lining, the higher pH of secretions in children with tracheostomy, and in particular, the regular interventions of suctioning and changing tubes.

Almost all studies in children with tracheostomy use solely tracheal aspirates to evaluate colonization or infection of the lower airway.10 However, this design does not allow the detection of an exogenous problem in a particular subset of patients. Both an oropharyngeal culture and tracheal aspirate have to be obtained as a pair of samples to distinguish the endogenous from the exogenous route of colonization or infection. Our data show that both samples are required to unravel the route of acquisition, because each requires a different infection control method. Oropharyngeal paste has been shown to control the endogenous route,9 whereas topical paste on the tracheostoma aims to control the exogenous route.

The topical application of polymyxin E and tobramycin is thought to act as a barrier to reduce the exogenous introduction of microorganisms into the lower airway. This method does not replace basic hygiene measures; it is, rather, an addition to it.

We believe that the intervention of topical antibiotics on the tracheostoma is promising in the prevention of the exogenous route. Further randomized trials are needed. If randomized trials prove this technique to be effective, we believe that the paste should only be applied for the immediate posttracheostomy period, inasmuch as patients are at their highest risk during that time.


   Footnotes
 
Abbreviations: CRP = C-reactive protein; MRSA = methicillin-resistant Staphylococcus aureus; PICU = pediatric ICU; PPM = potentially pathogenic microorganism

Received for publication June 9, 1999. Accepted for publication August 18, 1999.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Jarvis, WR (1987) Epidemiology of nosocomial infections in pediatric patients. Pediatr Infect Dis J 6,344-351[ISI][Medline]
  2. van Saene, HKF, Damjanovic, V, Murray, AE, et al (1996) How to classify infections in intensive care units: the carrier state, a criterion whose time has come? J Hosp Infect 33,1-12[CrossRef][ISI][Medline]
  3. Silvestri, L, Monti Bragadin, C, Milanese, M, et al (1999) Are most ICU infections really nosocomial? A prospective observational cohort study in mechanically ventilated patients. J Hosp Infect 42,125-133[CrossRef][ISI][Medline]
  4. Wiener, J, Weinstein, R (1994) Infection control methods. Neidermann, MS Sarosi, GA Glasroth, J eds. Respiratory infections: a scientific basis for management 1st ed. WB Saunders Philadelphia, PA.
  5. Levin, MH, Olson, B, Nathan, C, et al (1984) Pseudomonas in the sinks in an intensive care unit: relation to patients. J Clin Pathol 37,424-427[Abstract/Free Full Text]
  6. Morar, P, Singh, V, Jones, AS, et al (1998) Impact of tracheotomy on colonization and infection of lower airways in children requiring long-term ventilation: a prospective observational cohort study. Chest 113,77-85[Abstract/Free Full Text]
  7. Rogers JH. Tracheostomy and decannulation. In: Kerr AG, ed. Scott-Brown’s otolaryngology (vol 6). 6th ed. London: Butterworths, 1997; Ch 26
  8. Tym GM. Home tracheostomy care. In: Kerr AG, ed. Scott-Brown’s otolaryngology (vol 6). 6th ed. London: Butterworths, 1997; Ch 27
  9. Stoutenbeek, CP, van Saene, HKF, Liberati, A (1994) Prevention of respiratory tract infections in intensive care by selective decontamination of the digestive tract. Niederman, MS Sarosi, GA Glassroth, J eds. Respiratory infections 1st ed. ,579-594 WB Saunders Philadelphia, PA.
  10. Brook, I (1979) Bacterial colonization, tracheobronchitis, and pneumonia following tracheostomy and long-term intubation in pediatric patients. Chest 76,420-424[Abstract/Free Full Text]



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