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Original Article |

Alterations of the Oropharyngeal Microbial Flora After Adenotonsillectomy in Children:  A Randomized Controlled Trial FREE

Thuy My Le, MD; Maroeska M. Rovers, PhD; Birgit K. van Staaij, MD, PhD; Emma H. van den Akker, MD, PhD; Arno W. Hoes, MD, PhD; Anne G. M. Schilder, MD, PhD
[+] Author Affiliations

Author Affiliations: Julius Center for Health Sciences and Primary Care (Drs Le, Rovers, van Staaij, and Hoes) and Department of Otorhinolaryngology, Wilhelmina Children's Hospital (Drs Rovers, van den Akker, and Schilder), University Medical Center Utrecht, the Netherlands.


Arch Otolaryngol Head Neck Surg. 2007;133(10):969-972. doi:10.1001/archotol.133.10.969.
Text Size: A A A
Published online

Objectives  To determine whether the oropharyngeal microbial flora changes after adenotonsillectomy (ATY) in children with mild to moderate symptoms of throat infections or adenotonsillar hypertrophy and to relate these findings to recurrence of throat infections.

Design  Randomized controlled trial.

Setting  Twenty-three general hospitals and 3 academic centers.

Patients  Three hundred children aged 2 to 8 years who were selected for ATY because of recurrent throat infections (3-6 episodes per year) or obstructive complaints. Children with a history of 7 or more throat infections in the previous year and those with a high suspicion of obstructive sleep apnea according to current medical practice were excluded.

Interventions  Children were randomly assigned to either ATY or watchful waiting. Oropharyngeal swabs were taken at baseline and at 3 and 12 months after baseline.

Main Outcome Measures  The primary outcome measure was the prevalence of potentially pathogenic bacteria in the oropharynx at 3 and 12 months. The secondary outcome measure was the association between carriage of group A β-hemolytic streptococci (GABHS) at baseline and at 3 months' follow-up and the number of throat infections during the 12 months of follow-up.

Results  In the ATY group, prevalences of Haemophilus influenzae, GABHS, and Staphylococcus aureus decreased from 40%, 13%, and 5%, respectively, at baseline to respective levels of 24%, 0%, and 0% at 3 months and 26%, 0%, and 0% at 12 months. In the watchful waiting group, prevalences of H influenzae, GABHS, and S aureus did not change substantially. In neither the ATY nor the watchful waiting group was carriage of GABHS associated with recurrence of throat infections.

Conclusions  Adenotonsillectomy reduced oropharyngeal carriage of potential respiratory pathogens. Changes in the carriage rate of GABHS, however, had no beneficial effect on recurrence of throat infections.

Tonsils and adenoids are the largest components of the Waldeyer ring, the basic function of which is antibody formation.1 Since tonsils and adenoids are located at the entry of the gastrointestinal and respiratory tracts, they are considered the first line of defense against various microorganisms that enter the body through the mouth or nose.2 Adenoids and tonsils are active in young children, and therefore hypertrophy is common.3

Adenotonsillectomy (ATY) is a common therapeutic approach in children with adenotonsillar hypertrophy or recurrent throat infections.4,5 Besides viruses, the most important pathogens causing throat infections are group A β-hemolytic streptococci (GABHS).6 Other pathogens that play a role in upper respiratory tract infections are groups C and G β-hemolytic streptococci, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, and Streptococcus pneumoniae.610 The effect of ATY on carriage of these potential pathogens in the pharynx is not well established, nor is the effect of a potential reduction of GABHS on the incidence of throat infections.

The aim of this study was to evaluate alterations in the oropharyngeal microbial flora in children participating in a trial on the effectiveness of ATY. We compared the culture results of children assigned to ATY with those of children assigned to watchful waiting (WW), and we evaluated the association between carriage of GABHS and recurrence of throat infections.

PATIENTS

The present study is part of a randomized controlled trial investigating the effects of ATY in children. The inclusion and exclusion criteria and methods of this trial have been described in detail elsewhere.11 In short, the trial was conducted between March 2000 and February 2003. Participants were recruited by otolaryngologists in 23 general hospitals and 3 academic centers in the Netherlands. Otolaryngologists were asked to refer to the trial center every child aged 2 to 8 years selected for ATY because of recurrent throat infections (≥3 episodes per year) or obstructive complaints.

Excluded were children with (1) a history of 7 or more throat infections in the previous year or 5 or more in each of the 2 preceding years or 3 or more in each of the 3 preceding years (Paradise et al12 criteria); and/or (2) those with a high suspicion of obstructive sleep apnea (OSA) (Brouilette et al13 OSA score >3.5). These children were excluded because, as our research group showed in a previous study,5 of the children currently undergoing ATY in the Netherlands, 35% undergo the operation to treat such severe symptoms, whereas 65% undergo ATY for less frequent throat infections and milder symptoms of adenotonsillar hypertrophy. While frequent throat infections and OSA are generally considered adequate indications for ATY in children,12,14 there is no evidence for the benefits of ATY in a large proportion of children currently undergoing this procedure for milder symptoms.5,15,16 The primary aim of this trial, therefore, was to assess the effectiveness of ATY in children with mild to moderate symptoms of throat infection or adenotonsillar hypertrophy.11

Children whose parents gave informed consent were randomly assigned to 1 of 2 strategies: ATY within 6 weeks or WW. During the study, parents kept a diary of upper airway complaints in their child, such as sore throat and pain and/or difficulty with swallowing. They also measured their child's temperature daily with a validated infrared tympanic membrane thermometer.17 Both diary and thermometer data were collected by the study physician during scheduled follow-up visits at 3 and 12 months.

The study protocol was approved by the medical ethics committees of all participating hospitals.

BACTERIOLOGIC PROCEDURE

Throat swabs were taken at inclusion and during the follow-up visits at 3 and 12 months. Samples were obtained under direct light and depression of the tongue to avoid contamination by oral flora. When tonsils were present, their surface was sampled by firmly swabbing the mucosa of the left and the right tonsil with the same cotton swab. If tonsils had been removed, the mucosa of the tonsillar fossae was sampled similarly. The swabs were stabbed into a modified Stuart gel medium and transported to the Clinical Microbiology Laboratory of the University Medical Center Utrecht. Within 24 hours after collection, the samples were inoculated onto 5% sheep blood agar and chocolate agar plates. The plates were incubated both aerobically and under 5% carbon dioxide at 37°C and examined at 24 and 48 hours. Isolates were identified using conventional methods.18,19

The following potentially pathogenic bacteria were identified: GABHS, group C β-hemolytic streptococci, group G β-hemolytic streptococci, H influenzae, S aureus, M catarrhalis, and S pneumoniae.

OUTCOME

The primary outcome of this study was the prevalence of these potentially pathogenic microorganisms in the oropharynx at 3 and 12 months after baseline. Furthermore, positive culture results for GABHS at baseline and at 3 months were related to the incidence of throat infections during the 12 months of follow-up. A throat infection was defined as sore throat and/or pain and/or difficulty with swallowing, as indicated in the diary, in combination with fever (temperature ≥38.0°C as measured by the tympanic thermometer).11

STATISTICAL ANALYSIS

The microbial results and use of antibiotics in the ATY and WW groups were compared with χ2 and Fisher exact tests. Analyses were performed according to the intention-to-treat principle. To study the effect of the microbial findings on recurrence of throat infections in both the ATY and WW group, we compared the median incidence of throat infections during 12 months of follow-up in children with a positive culture for GABHS at baseline or at 3 months vs the median incidence in children with a negative throat culture at these visits. Differences were tested with the Mann-Whitney U test, as data were not normally distributed. All analyses were performed with SPSS software, version 12 (SPSS Inc, Chicago, Illinois).

PATIENTS

In total, 300 children were randomized: 151 were allocated to the ATY group, 149 to the WW group. Baseline characteristics did not differ between the 2 groups: the mean age was 54 months; the median number of throat infections in the year before trial entry was 3; and the median OSA score was −1.7 in both groups (Table 1).

Table Graphic Jump LocationTable 1. Baseline Demographic and Clinical Characteristics of Children Randomly Assigned to Adenotonsillectomy or a Watchful Waiting Strategya

Fifty children (34%) changed from the WW to the ATY group because of persistent tonsil-related complaints. Seven children in the ATY group (5.5%) did not undergo ATY because their parents declined permission for surgery after randomization to the ATY group.

At baseline, 7 children in the ATY group (5.5%) and 16 in the WW group (13%) (P = .05) had used antibiotics in the 2 weeks before their throat culture was taken. At 3 months, these respective figures were n = 4 (3.0%) and n = 6 (4.5%) (P = .54); and at 12 months, n = 1 (0.8%) and n = 4 (3.6%) (P = .20).

OROPHARYNGEAL MICROBIAL FLORA

In the ATY group, prevalences of H influenzae, GABHS, and S aureus decreased from 40%, 13%, and 5% at baseline to 24%, 0%, and 0% at 3 months and 26%, 0%, and 0% at 12 months, respectively. In the WW group, prevalences of H influenzae, GABHS, and S aureus did not change substantially: 39%, 7%, and 6% at baseline; 38%, 6%, and 7% at 3 months; and 40%, 8%, and 8% at 12 months, respectively (Table 2).

Table Graphic Jump LocationTable 2. Potential Bacterial Pathogens Isolated From the Oropharynx in Children in the Adenotonsillectomy and Watchful Waiting Groupsa
OROPHARYNGEAL MICROBIAL FLORA AND THROAT INFECTIONS

In the ATY group, the median number of throat infections during the 12 months of follow-up was 1, both among the children with a positive result of GABHS culture (range, 0-3 infections) and those with negative GABHS findings at baseline or at 3 months (range, 0-4 infections) (P = .76). In the WW group, the median number of throat infections was 1 (range, 0-3 infections) among children with positive GABHS findings and 0 (range, 0-4 infections) among those with negative findings (P = .86).

To our knowledge, this is the first large randomized controlled trial of ATY in children to evaluate the effect of surgery on the oropharyngeal microbial flora and to relate these findings to clinical effects. It shows that in children undergoing ATY for mild to moderate symptoms of throat infections or adenotonsillar hypertrophy, surgery is associated with a reduction in carriage of potential respiratory pathogens in the oropharynx. A decrease in the carriage rate of GABHS, however, had no beneficial effect on recurrence of throat infections.

In a previous publication, our research group19 showed that the tonsillar flora of the children selected for ATY and participating in this trial differed only slightly from children without symptoms of tonsillar disease. This suggests that oropharyngeal carriage itself does not play a major role in the susceptibility of children to throat infections.19

Our results are in agreement with those of others showing reduced oropharyngeal carriage of potential pathogens after tonsillectomy.2022 These studies, however, had smaller sample sizes,21,22 shorter follow-up periods,2022 and all lacked a randomly assigned control group.2022

These results should be interpreted in the light of several limitations. First, children with very frequent (≥7 per year) throat infections or OSA were excluded from our trial because these symptoms are generally considered adequate indications for surgery.11 Our results are therefore only generalizable to children with milder symptoms of throat infections or adenotonsillar hypertrophy.

Second, 50 children (34%) changed from the WW to the ATY group, whereas 7 children in the ATY group (5.5%) did not undergo ATY. Since we found that ATY reduced oropharyngeal carriage of potentially pathogenic bacteria, our intention-to-treat analytic strategy may have resulted in an underestimation of the number ofpotentially pathogenic bacteria in the WW group. We therefore also performed a per-protocol analysis including only the children who were compliant to the randomization; ie, children who changed from the WW group to the ATY group or from the ATY group to the WW group were excluded. The results of this analysis, however, did not differ substantially from those of the intention-to-treat analysis.

In conclusion, ATY was associated with a reduction of oropharyngeal carriage of potential respiratory pathogens. Changes in the carriage rate of GABHS, however, had no beneficial effect on recurrence of throat infections.

Correspondence: Anne G. M. Schilder, MD, PhD, Department of Otorhinolaryngology, E 04.140.5, Wilhelmina Children's Hospital, University Medical Center Utrecht, PO Box 85090, 3590 AB Utrecht, the Netherlands (a.schilder@umcutrecht.nl).

Submitted for Publication: October 19, 2006; final revision received January 22, 2007; accepted February 7, 2007.

Author Contributions: Dr Schilder had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Rovers, van Staaij, van den Akker, Hoes, and Schilder. Acquisition of data: Rovers, van Staaij, van den Akker, and Schilder. Analysis and interpretation of data: Le, Rovers, Hoes, and Schilder. Drafting of the manuscript: Le, Rovers, and Schilder. Critical revision of the manuscript for important intellectual content: Rovers, van Staaij, van den Akker, Hoes, and Schilder. Statistical analysis: Rovers, van Staaij, and Hoes. Obtained funding: Hoes and Schilder. Administrative, technical, and material support: van den Akker. Study supervision: Rovers, Hoes, and Schilder.

Financial Disclosure: None reported.

Funding/Support: This study was funded by a grant from the Dutch Health Care Insurance Board (OG-99-060), Diemen, the Netherlands.

Additional Contributions: We thank the participants and their parents and our colleagues and nurses in the participating hospitals; Nelly van Eden provided secretarial support and Frank Leus, data management.

Perry  MWhyte  A Immunology of the tonsils. Immunol Today 1998;19 (9) 414- 421
PubMed Link to Article
Richtsmeier  WJShikhani  AH The physiology and immunology of the pharyngeal lymphoid tissue. Otolaryngol Clin North Am 1987;20 (2) 219- 228
PubMed
Potsic  WP Assessment and treatment of adenotonsillar hypertrophy in children. Am J Otolaryngol 1992;13 (5) 259- 264
PubMed Link to Article
Nave  HGebert  APabst  R Morphology and immunology of the human palatine tonsil. Anat Embryol (Berl) 2001;204 (5) 367- 373
PubMed Link to Article
van den Akker  EHSchilder  AGKemps  YJvan Balen  FAHordijk  GJHoes  AW Current indications for (adeno)tonsillectomy in children: a survey in the Netherlands. Int J Pediatr Otorhinolaryngol 2003;67 (6) 603- 607
PubMed Link to Article
Gunnarsson  RKHolm  SESoderstrom  M The prevalence of potential pathogenic bacteria in nasopharyngeal samples from individuals with a respiratory tract infection and a sore throat: implications for the diagnosis of pharyngotonsillitis. Fam Pract 2001;18 (3) 266- 271
PubMed Link to Article
Bluestone  CDStephenson  JSMartin  LM Ten-year review of otitis media pathogens. Pediatr Infect Dis J 1992;11 (8) (suppl)S7- S11
PubMed Link to Article
Klein  JO Otitis media. Clin Infect Dis 1994;19 (5) 823- 833
PubMed Link to Article
Piccirillo  JF Clinical practice: acute bacterial sinusitis. N Engl J Med 2004;351 (9) 902- 910
PubMed Link to Article
Brook  I Microbiology and antimicrobial management of sinusitis. J Laryngol Otol 2005;119 (4) 251- 258
PubMed Link to Article
van Staaij  BKVan Den Akker  EHRovers  MMHordijk  GJHoes  AWSchilder  AG Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open, randomised controlled trial. BMJ 2004;329 (7467) 651
PubMed Link to Article
Paradise  JLBluestone  CDBachman  RZ  et al.  Efficacy of tonsillectomy for recurrent throat infection in severely affected children: results of parallel randomized and nonrandomized clinical trials. N Engl J Med 1984;310 (11) 674- 683
PubMed Link to Article
Brouilette  RHanson  DDavid  R  et al.  A diagnostic approach to suspected obstructive sleep apnea in children. J Pediatr 1984;105 (1) 10- 14
PubMed Link to Article
Flanary  VA Long-term effect of adenotonsillectomy on quality of life in pediatric patients. Laryngoscope 2003;113 (10) 1639- 1644
PubMed Link to Article
Capper  RCanter  RJ Is there agreement among general practitioners, paediatricians and otolaryngologists about the management of children with recurrent tonsillitis? Clin Otolaryngol Allied Sci 2001;26 (5) 371- 378
PubMed Link to Article
Donnelly  MJQuraishi  MSMcShane  DP Indications for paediatric tonsillectomy GP versus consultant perspective. J Laryngol Otol 1994;108 (2) 131- 134
PubMed Link to Article
van Staaij  BKRovers  MMSchilder  AGHoes  AW Accuracy and feasibility of daily infrared tympanic membrane temperature measurements in the identification of fever in children. Int J Pediatr Otorhinolaryngol 2003;67 (10) 1091- 1097
PubMed Link to Article
Balows  AAHausler  JWJHermann  KL Manual of Clinical Microbiology. 5th ed. Washington, DC: American Society for Microbiology; 1991
Van Staaij  BKVan Den Akker  EHDe Haas Van Dorsser  EHFleer  AHoes  AWSchilder  AG Does the tonsillar surface flora differ in children with and without tonsillar disease? Acta Otolaryngol 2003;123 (7) 873- 878
PubMed Link to Article
García Callejo  FJVlert Vila  MMOrts Alborch  MHPardo Mateu  LMarco Algarra  J Effects of adenoidectomy and tonsillectomy on nasopharyngeal and oropharyngeal bacterial flora. Acta Otorrinolaringol Esp 1997;48 (6) 467- 472
PubMed
Manolis  ETsakris  AKandiloros  D  et al.  Alterations to the oropharyngeal and nasopharyngeal microbial flora of children after tonsillectomy and adenoidectomy. J Laryngol Otol 1994;108 (9) 763- 767
PubMed Link to Article
Talaat  AMBahgat  YSel-Ghazzawy  EElwany  S Nasopharyngeal bacterial flora before and after adenoidectomy. J Laryngol Otol 1989;103 (4) 372- 374
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Baseline Demographic and Clinical Characteristics of Children Randomly Assigned to Adenotonsillectomy or a Watchful Waiting Strategya
Table Graphic Jump LocationTable 2. Potential Bacterial Pathogens Isolated From the Oropharynx in Children in the Adenotonsillectomy and Watchful Waiting Groupsa

References

Perry  MWhyte  A Immunology of the tonsils. Immunol Today 1998;19 (9) 414- 421
PubMed Link to Article
Richtsmeier  WJShikhani  AH The physiology and immunology of the pharyngeal lymphoid tissue. Otolaryngol Clin North Am 1987;20 (2) 219- 228
PubMed
Potsic  WP Assessment and treatment of adenotonsillar hypertrophy in children. Am J Otolaryngol 1992;13 (5) 259- 264
PubMed Link to Article
Nave  HGebert  APabst  R Morphology and immunology of the human palatine tonsil. Anat Embryol (Berl) 2001;204 (5) 367- 373
PubMed Link to Article
van den Akker  EHSchilder  AGKemps  YJvan Balen  FAHordijk  GJHoes  AW Current indications for (adeno)tonsillectomy in children: a survey in the Netherlands. Int J Pediatr Otorhinolaryngol 2003;67 (6) 603- 607
PubMed Link to Article
Gunnarsson  RKHolm  SESoderstrom  M The prevalence of potential pathogenic bacteria in nasopharyngeal samples from individuals with a respiratory tract infection and a sore throat: implications for the diagnosis of pharyngotonsillitis. Fam Pract 2001;18 (3) 266- 271
PubMed Link to Article
Bluestone  CDStephenson  JSMartin  LM Ten-year review of otitis media pathogens. Pediatr Infect Dis J 1992;11 (8) (suppl)S7- S11
PubMed Link to Article
Klein  JO Otitis media. Clin Infect Dis 1994;19 (5) 823- 833
PubMed Link to Article
Piccirillo  JF Clinical practice: acute bacterial sinusitis. N Engl J Med 2004;351 (9) 902- 910
PubMed Link to Article
Brook  I Microbiology and antimicrobial management of sinusitis. J Laryngol Otol 2005;119 (4) 251- 258
PubMed Link to Article
van Staaij  BKVan Den Akker  EHRovers  MMHordijk  GJHoes  AWSchilder  AG Effectiveness of adenotonsillectomy in children with mild symptoms of throat infections or adenotonsillar hypertrophy: open, randomised controlled trial. BMJ 2004;329 (7467) 651
PubMed Link to Article
Paradise  JLBluestone  CDBachman  RZ  et al.  Efficacy of tonsillectomy for recurrent throat infection in severely affected children: results of parallel randomized and nonrandomized clinical trials. N Engl J Med 1984;310 (11) 674- 683
PubMed Link to Article
Brouilette  RHanson  DDavid  R  et al.  A diagnostic approach to suspected obstructive sleep apnea in children. J Pediatr 1984;105 (1) 10- 14
PubMed Link to Article
Flanary  VA Long-term effect of adenotonsillectomy on quality of life in pediatric patients. Laryngoscope 2003;113 (10) 1639- 1644
PubMed Link to Article
Capper  RCanter  RJ Is there agreement among general practitioners, paediatricians and otolaryngologists about the management of children with recurrent tonsillitis? Clin Otolaryngol Allied Sci 2001;26 (5) 371- 378
PubMed Link to Article
Donnelly  MJQuraishi  MSMcShane  DP Indications for paediatric tonsillectomy GP versus consultant perspective. J Laryngol Otol 1994;108 (2) 131- 134
PubMed Link to Article
van Staaij  BKRovers  MMSchilder  AGHoes  AW Accuracy and feasibility of daily infrared tympanic membrane temperature measurements in the identification of fever in children. Int J Pediatr Otorhinolaryngol 2003;67 (10) 1091- 1097
PubMed Link to Article
Balows  AAHausler  JWJHermann  KL Manual of Clinical Microbiology. 5th ed. Washington, DC: American Society for Microbiology; 1991
Van Staaij  BKVan Den Akker  EHDe Haas Van Dorsser  EHFleer  AHoes  AWSchilder  AG Does the tonsillar surface flora differ in children with and without tonsillar disease? Acta Otolaryngol 2003;123 (7) 873- 878
PubMed Link to Article
García Callejo  FJVlert Vila  MMOrts Alborch  MHPardo Mateu  LMarco Algarra  J Effects of adenoidectomy and tonsillectomy on nasopharyngeal and oropharyngeal bacterial flora. Acta Otorrinolaringol Esp 1997;48 (6) 467- 472
PubMed
Manolis  ETsakris  AKandiloros  D  et al.  Alterations to the oropharyngeal and nasopharyngeal microbial flora of children after tonsillectomy and adenoidectomy. J Laryngol Otol 1994;108 (9) 763- 767
PubMed Link to Article
Talaat  AMBahgat  YSel-Ghazzawy  EElwany  S Nasopharyngeal bacterial flora before and after adenoidectomy. J Laryngol Otol 1989;103 (4) 372- 374
PubMed Link to Article

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