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Increased recovery of Moraxella catarrhalis and Haemophilus influenzae in association with group A ß-haemolytic streptococci in healthy children and those with pharyngo-tonsillitis

Department of Pediatrics, Georgetown University, School of Medicine, Washington, DC, USA

Correspondence
Itzhak Brook
ib6{at}georgetown.edu

Received 9 September 2005
Accepted 22 March 2006

Abbreviations: APT, acute pharyngo-tonsillitis; BLPB, ß-lactamase-producing bacteria; GABHS, group A ß-haemolytic streptococci.

	INTRODUCTION

TOP INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Acute pharyngo-tonsillitis (APT) is a common infection, especially in children and young adults. The diagnosis of bacterial APT generally requires the consideration of group A ß-haemolytic streptococci (GABHS) infection. However, numerous other bacteria (including Moraxella catarrhalis and Haemophilus influenzae) can be recovered from these tonsils alone or in combination with GABHS.

GABHS is a common colonizer of the pharynx of children. These individuals are sometimes labelled as ‘carriers' of GABHS. Even though the carriage of GABHS is generally not associated with any adverse effects, the recovery of GABHS from a child with symptoms of APT may confirm the clinical diagnosis. Furthermore, individuals colonized with GABHS can serve as a source of spread of this organism to their contacts. In addition to GABHS, numerous other aerobic and anaerobic bacteria, alone or in combination with GABHS, can be recovered from the pharynx of children (Brook, 2005).

Several studies suggest that the colonization of the tonsils by GABHS and certain other aerobic and anaerobic bacterial species may contribute to the inflammatory process and the failure of penicillin therapy (Brook, 2005). A mutual symbiotic enhancement of growth of GABHS in the presence of other aerobic and anaerobic bacteria has been demonstrated in an animal model (Brook & Gillmore, 1996). Such a synergistic relationship may also exist between these organisms and GABHS in patients with tonsillitis. An example of a potential synergistic relationship is the ability of M. catarrhalis to increase the adherence of GABHS to human epithelial cells through species-specific co-aggregation (Lafontaine et al., 2004).

Several of the organisms that are isolated from the tonsils can produce the enzyme ß-lactamase. These include M. catarrhalis, H. influenzae and Staphylococcus aureus. This enzyme can inactivate penicillin and contribute to the failure of this agent to eradicate GABHS from infected tonsils (Brook, 1984).

This study investigated whether the recovery of M. catarrhalis, H. influenzae, Staph. aureus and Streptococcus pneumoniae is associated with GABHS in healthy children and those with APT.

	METHODS

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Patients. The population studied was middle class, residing in suburban locations in the vicinity of Washington, DC. Patients seen consecutively for APT and those seen consecutively for their annual physical examination were included in the study. APT was defined as acute onset of sore throat plus at least one of the following: anterior cervical adenitis, temperature >38.3 °C (101 °F), pharyngeal or tonsillar exudates, or pharyngeal injection. The study was granted an Institutional Review Board approval.

A total of 548 children with APT were evaluated. The median age of the children was 7 years and 4 months (range, 2.5–14 years). Past medical history, including antimicrobial therapy and day-care attendance, was obtained by using a questionnaire and reviewing medical records. Those who received antimicrobial therapy or who had suffered from GABHS APT in the previous 3 months were excluded.

A total of 866 healthy children were evaluated as control subjects. The median age of the children was 6 years and 10 months (range, 2.5–14 years). Past medical history, including antimicrobial therapy and day-care attendance, was obtained by using a questionnaire and reviewing medical records. Excluded were those who had received antimicrobial therapy or suffered from GABHS APT in the previous 3 months.

Bacteriological methods. Pharyngo-tonsillar cultures were obtained from all children with a sterile cotton swab. The swab was placed in a transport system for aerobic bacteria (Culturette, Marion Scientific) and inoculated within 24 h of collection. Sheep blood (5 %), chocolate and MacConkey agar plates were inoculated for the isolation of aerobic organisms. Plates were incubated at 37 °C aerobically (MacConkey) and in 5 % carbon dioxide (blood and chocolate), and examined at 24 and 48 h. The organisms were identified by conventional methods (Murray et al., 1995). GABHS were identified by determining bacitracin sensitivity and by serologic grouping by Phadebact coagglutination (Pharmacia Diagnostics). ß-Lactamase activity was determined by chromogenic cephalosporin analogue 87/312 methodology (O'Callaghan et al., 1972). Statistical analysis was done using Fishers exact test. P values were two-sided. Comparisons were made using StatXact software.

	RESULTS

TOP INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Children with APT

GABHS was recovered from 112 (20.4 %) children. GABHS was isolated in the absence of M. catarrhalis, H. influenzae, Staph. aureus and Strep. pneumoniae in 34 instances, in association with one of the other isolates in 64 cases, with two others in ten, and with three others in four children.

Thirty-two of 114 H. influenzae isolates were recovered in association with GABHS (29 % of all patients who had GABHS) and 82 were isolated without GABHS (19 % of all patients who had no GABHS) (P=0.0267). Twenty-five of the 69 M. catarrhalis isolates were recovered in association with GABHS (22 % of all patients who had GABHS) and 44 were isolated without GABHS (10 % of all patients who had no GABHS) (P=0.0012) (Table 1). In contrast there was no association between the isolation of GABHS and the recovery of Staph. aureus or Strep. pneumoniae.

Healthy children

GABHS was recovered from 104 (12 %) of the 866 children. GABHS was isolated without any of the other four organisms in 32 instances, in association with one of the other isolates in 62 cases, with two others in seven, and with three others in four children.

Of the 69 M. catarrhalis isolates, 24 were recovered in association with GABHS (23 % of all patients who had GABHS) and 80 were isolated without GABHS (10 % of all patients who had no GABHS) (P=0.006) (Table 2). In contrast there was no association between the isolation of GABHS and the recovery of H. influenzae, Staph. aureus or Strep. pneumoniae.

	DISCUSSION

TOP INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
This study demonstrates an association between the recovery of GABHS and H. influenzae and M. catarrhalis from pharyngo-tonsillar cultures of children with APT, and M. catarrhalis from pharyngo-tonsillar cultures of healthy children. H. influenzae and M. catarrhalis have been recovered in 10–20 % of acutely (Brook, 1985), recurrently (Stjernquist-Desatnik et al., 1990) and chronically (Brook et al., 1995) inflamed tonsils. However, this study is the first to associate their isolation in conjunction with the recovery of GABHS.

The increased isolation of H. influenzae (in APT only) and M. catarrhalis in association with GABHS may be due to a synergistic relationship between these organisms (Brook & Gillmore, 1996; Lafontaine et al., 2004). The ability of H. influenzae and M. catarrhalis to produce the enzyme ß-lactamase may also make them, as well as GABHS, more resistant to eradication by penicillin and contribute to failure of penicillin therapy. This may be due to the ability of ß-lactamase to inactivate the penicillin in the tonsillar tissues (Brook, 1984).

We have previously demonstrated an association between the recovery of these, as well as other BLPB, and an increased failure of penicillin to eradicate GABHS (Brook, 1985). We evaluated 98 children who had acute tonsillitis due to GABHS and were treated for 10 days with orally administered penicillin. On the basis of bacteriologic results, 62 patients were considered ‘cured’ (group A) and 36 ‘failed’ (group B) following therapy. Before therapy, 18 isolates of BLPB were detected in 16 (26 %) children in group A; after therapy 30 BLPB were detected in 19 (30 %) children. In contrast, before therapy, 40 BLPB were recovered from 25 (69 %) children in group B; this number increased to 62 BLPB in 31 (86 %) of those children.

An indirect support for the potential synergistic relationship between GABHS and H. influenzae and M. catarrhalis is the better clinical efficacy, as compared to penicillin, of second-generation extended-spectrum, and third-generation cephalosporins (Casey & Pichichero, 2004), as well as the combination of amoxycillin and clavulanate (Brook, 1989; Kaplan & Johnson, 1988), in eradicating GABHS pharyngo-tonsillitis. The superior efficacy of these agents compared to penicillin may be due to their activity against GABHS, as well as ß-lactamase-producing H. influenzae and M. catarrhalis.

Further studies are warranted to evaluate the nature of the interactions between GABHS and H. influenzae and M. catarrhalis, and whether antimicrobials active against these organisms are more effective in eradication of GABHS infection.

	ACKNOWLEDGEMENTS

 
The authors acknowledge the statistical analysis by William E. Jackson.

	REFERENCES

TOP INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

 
Brook, I. (1984). The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection. Rev Infect Dis 6, 601–607.[Medline]

Brook, I. (1985). Role of beta-lactamase-producing bacteria in the failure of penicillin to eradicate group A streptococci. Pediatr Infect Dis 4, 491–495.[Medline]

Brook, I. (1989). Treatment of patients with acute recurrent tonsillitis due to group A beta-haemolytic streptococci: a prospective randomized study comparing penicillin and amoxycillin/clavulanate potassium. J Antimicrob Chemother 24, 227–233.[Abstract/Free Full Text]

Brook, I. (2005). The role of anaerobic bacteria in tonsillitis. Int J Pediatr Otorhinolaryngol. 69, 9–19.[CrossRef][Medline]

Brook, I. & Gillmore, J. D. (1996). Enhancement of growth of group A beta-hemolytic streptococci in mixed infections with aerobic and anaerobic bacteria. Clin Microbiol Infect 1, 179–182.[Medline]

Brook, I., Yocum, P. & Foote, P. A. (1995). Changes in the core tonsillitis bacteriology of recurrent tonsillitis: 1977–1980. Clin Infect Dis 21, 171–176.[Medline]

Casey, J. R. & Pichichero, M. E. (2004). Meta-analysis of cephalosporins versus penicillin for treatment of group A streptococcal tonsillopharyngitis in adults. Clin Infect Dis 38, 1526–1534.[CrossRef][Medline]

Kaplan, E. L. & Johnson, D. R. (1988). Eradication of group A streptococcus from the upper respiratory tract by amoxicillin with clavulanate after oral penicillin treatment failure. J Pediatr 113, 400–403.[CrossRef][Medline]

Lafontaine, E. R., Wall, D., Vanlerberg, S. L., Donabedian, H. & Sledjeski, D. D. (2004). Moraxella catarrhalis coaggregates with Streptococcus pyogenes and modulates interactions of S. pyogenes with human epithelial cells. Infect Immun 72, 6689–6693.[Abstract/Free Full Text]

Murray, P. R., Baron, E. J., Pfaller, M. A., Tenover, F. C. & Yolken, R. H. (1995). Manual of Clinical Microbiology, 5th edn. Washington, DC: American Society for Microbiology.

O'Callaghan, C. H., Morris, A., Kirby, S. M. & Shingler, A. H. (1972). Novel method for detection of beta-lactamase by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother 1, 283–288.[Abstract/Free Full Text]

Stjernquist-Desatnik, A., Prellner, K. & Schalen, C. (1990). Colonization by Haemophilus influenzae and group A streptococci in recurrent acute tonsillitis and in tonsillar hypertrophy. Acta Otolaryngol 109, 314–319.[Medline]

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