The role of anaerobic bacteria in tonsillitis is hard to elucidate because these organisms are normally prevalent on the surface of the tonsils and pharynx as well as in the core of tonsils and adenoids, so that cultures taken directly, from these areas are difficult to interpret. Anaerobic bacteria are part of the normal on pharyngeal flora and are capable of interfering with the in-vitro growth of GABHS as well as other potential pathogens. The number of anaerobes in the normal oropharyngeal flora outnumbers the number of aerobes at a ratio of 100:1 and they can reach 10 logs of organism /gram.
More about anaerobes and anaerobic infections can be found at the website devoted to anaerobic infections.
Anaerobes predominate in the oral flora
The pathogenic potential of anaerobes is realized in a variety of localized clinical infections proximal to the tonsils which include: dental,1 peritonsillar 2 and retropharyngeal 3 abscesses, cervical adenitis,4 chronic otitis media and sinusitis,5 and mastoiditis.6
Many of the Gram-negative anaerobic bacilli (GNAB) that are isolated from the tonsillar core can produce the enzyme beta-lactamase. Beta-lactamase-producing strains of Bacteroides fragilis group, Fusobacterium spp., H. influenzae and S. aureus were isolated from the tonsils of 73% to 80% of children with GABHS recurrent tonsillitis7-11 and from 40% of children of non-GABHS tonsillitis (NST).12 The production of beta-lactamase has important implications for antimicrobial therapy. These organisms could degrade penicillin in the area of the infection, thereby protecting not only themselves but also penicillin-sensitive associated pathogens. Thus, penicillin therapy directed against a susceptible pathogen might be rendered ineffective by the presence of beta-lactamase-producing bacteria (BLPB). This phenomenon may explain the growing failure of penicillin in eradicating GABHS tonsillitis.13 The possibility that penicillin-resistant anaerobic bacteria may protect pathogenic organisms has been extensively studied. 7-11
The anaerobic species that have been implicated in tonsillitis are pigmented Prevotella and Porphyromonas, Fusobacterium and Actinomyces spp. The possible role of anaerobes in the acute inflammatory process in the tonsils is supported by several clinical and scientific observations: anaerobes have been isolated from the cores of tonsils of children and adults with recurrent GABHS7 and NST12,14 and peritonsillar2 and retropharyngeal3 abscesses in many cases without any aerobic bacteria, their recovery as pathogens in well-established anaerobic infections of the tonsils (Vincent's angina),15 the increased recovery rate of encapsulated pigmented Prevotella and Porphyromonas spp. in acutely inflamed tonsils,16 and the response to antibiotics in patients with NST.17-22
GABHS interacts with other bacteria in the tonsillar crypts
Additional support for the role of anaerobic bacteria in tonsillitis is the demonstration of an immune response against Prevotella intermedia in patients with recurrent NST;23 and an immune response against P. intermedia and Fusobacterium nucleatum in patients who recovered from peritonsillar cellulitis or abscesses24 and infectious mononucleosis25 and acute NST and GABHS tonsillitis.26
GABHS interacts with other bacteria in the tonsillar crypts
Additional support for the role of anaerobic bacteria in tonsillitis is the demonstration of an immune response against Prevotella intermedia in patients with recurrent NST;23 and an immune response against P. intermedia and Fusobacterium nucleatum in patients who recovered from peritonsillar cellulitis or abscesses24 and infectious mononucleosis25 and acute NST and GABHS tonsillitis.26
This page summarizes the information that supports the potential importance of anaerobic bacteria in tonsillitis.
Anaerobes as interfering bacteria
Bacterial interference can play a major role in the maintenance the normal mucous membranes flora, by preventing colonization and subsequent invasion by potential pathogenic bacteria.27 This phenomenon is most important in preventing certain bacterial infections. Anaerobic bacteria with interfering capabilities with the in-vitro growth of GABHS, are part of the normal oropharyngeal flora.
We compared28 the frequency of recovery of aerobic and anaerobic bacteria with interfering capability for GABHS from the tonsils of children with and without the history of recurrent GABHS pharyngo-tonsillitis. Tonsillar cultures were taken from 20 children with and 20 without the history of recurrent GABHS pharyngo-tonsillitis. Eleven aerobic and anaerobic isolates with interfering capability for GABHS were recovered from 6 of the 20 (30%) children with recurrent GABHS tonsillitis, and 40 such organisms were isolated from 17 of the 20 (85%) without recurrences (p < 0.01). The interfering organisms included aerobic (alpha and non-hemolytic streptococci), and anaerobic organisms (Prevotella and Peptostreptococcus spp.). The study illustrates that the tonsils of children with the history of recurrent GABHS infection contain less aerobic and anaerobic bacteria with interfering capability of GABHS than those without that history. It also suggests that the presence of these interfering bacteria may play a role in preventing GABHS infection.
Most peritonsillar abscesses ( PA ) are polymicrobial; the average number of isolates is 5 (range 1 to 10).2,8,29-33 The predominant anaerobic organisms isolated in peritonsillar abscesses are Prevotella, Porphyromonas, Fusobacterium and Peptostreptococcus spp.; aerobic organisms are GABHS (Streptococcus pyogenes), S. aureus and H. influenzae. Anaerobes can be isolated from most abscesses whenever appropriate techniques for their cultivation have been employed,29 while GABHS is isolated in only about one-third of cases.2,31
Peritonsillar abscess
Hansen34 studied 153 aspirates from PA and isolated 151 strains of GNAB, including, Bacteroides funduliformis, fusiform bacilli, and B. fragilis. Hallander, et al35 recovered anaerobic bacteria from 26 of 30 patients. These included Bacteroides spp., Fusobacterium spp,, Peptostreptococcus spp., microaerophilic streptococci, veillonellae, and bifidobacteria. Sprinkle, et al36 isolated anaerobes from four of six patients with peritonsillar abscess. Anaerobes only were found in one instance, and the others yielded mixed aerobic and anaerobic flora. Lodenkämper and Stienen37 isolated Bacteroides spp. from six patients with retro-tonsillar abscess, and Baba, et al38 recovered Peptostreptococcus spp from four patients.
Ophir et al.39 isolated eight Bacteriodes spp. from 62 patients. Aspiration of PA performed in 16 children was reported by Brook.2 There were 91 anaerobic and 32 aerobic isolates (Table 1). The predominant organisms were pigmented Prevotella and Porphyromonas spp, anaerobic Gram-positive cocci, Fusobacterium spp., gamma-hemolytic streptococci, alpha-hemolytic streptococci, GABHS, Haemophilus spp., clostridia, and S. aureus. Thirteen BLPB were recovered from 11 patients (68%). These included all three isolates of S. aureus, eight (35%) of the 23 Prevotella melaninogenica, and two (40%) of the five Prevotella oralis.
Table 1. Bacteria isolated in 16 children with peritonsillar abscesses.2
Aerobic and facultative isolates
|
No. of isolates
|
Anaerobic isolates
|
No. of isolates
|
Gram-positive cocci (total)
|
27
|
Anaerobic cocci
|
22
|
Group A beta-hemolytic streptococci
|
4
|
Gram-positive bacilli (total)
|
12
|
Clostridium spp.
|
3
| ||
S. aureus
|
3
| ||
Gram-negative bacilli (total)
|
5
|
Gram-negative bacilli (total)
|
57
|
H. influenzae
|
4
|
Fusobacterium spp.
|
15
|
Total no. of aerobes
|
32
|
Bacteroides spp.
|
14
|
pigmented Prevotella and Porphyromonas spp.
|
23
| ||
P. oralis
|
5
| ||
Total no. of anaerobes
|
91
| ||
Note: Only the important pathogens are listed in detail. The total number of the groups of organisms is represented.
We evaluated 34 aspirates of pus obtained from adults and children with PA for aerobic and anaerobic bacteria.40 A total 107 isolates (58 anaerobic and 49 aerobic and facultative) were recovered. Anaerobic bacteria only were detected in 6 (18%) patients, aerobic and facultatives in 2 (6%), and mixed aerobic and anaerobic flora in 26 (76%). Single isolates were recovered in 4 infections, 2 of which were GABHS and 2 were anaerobic bacteria. The predominant bacterial isolates were S. aureus (6 isolates), GNAB (21, including 15 pigmented Prevotella and Porphyromonas spp.), and Peptostreptococcus spp. (16) and GABHS (10). BLPB were recovered from 13 (52%) of 25 specimens tested.
Aspirated pus samples from 124 patients with PA were cultured quantitatively for aerobic and anaerobic bacteria by Jousimies-Somer et al.41 Of the 550 isolates obtained ( 4.4 per patient), 143 were aerobes (representing 16 species or groups) and 407 were anaerobes (representing 40 species or groups). Aerobes were isolated from 86% of patients-alone in 20 cases and together with anaerobes in 87. The predominant aerobic isolates were GABHS (isolated from 45% of patients), Streptococcus milleri group organisms (27%), H influenzae (11%), and viridans streptococci (11%). Anaerobes were isolated from 82% of the samples and as a sole finding from 15. Fusobacterium necrophorum and P. melaninogenica were both isolated from 38% of patients, Prevotella intermedia from 32%, Peptostreptococcus micros from 27%, Fusobacterium nucleatum from 26%, and Actinomyces odontolyticus from 23%. The rate of previous tonsillar and peritonsillar infections was lowest (25%) among patients infected with GABHS and highest (52%) among those infected with F. necrophorum (P < .01). Recurrences and/or related tonsillectomies were more common among patients infected with F. necrophorum than among those infected with GABHS (57% vs. 19%; P < .0001) or with S. milleri group(43% vs. 19%; P < .05). Beta-lactamase was produced by only 38% of the 73 isolates of Prevotella spp. tested; however, 56% of the 36 patients studied harbored one or more such strains.
Mitchelmore et al studied pus aspirated from 53 PA for aerobic and anaerobic bacteria.42 Cultures were positive in 45 (85%) instances: 7 yielded aerobic organisms, mainly GABHS, and 38 yielded anaerobic organisms. Most anaerobes were recovered mixed with other aerobic and anaerobic organisms, and only in two cases F. necrophorum was isolated in pure culture. P. micros and S. milleri were the predominant isolates in this study. BLPB were recovered from ten patients (19%).
Numerous studies that utilized adequate methodology highlight the polymicrobial aerobic-anaerobic nature and importance of anaerobic bacteria in PA. Use of antimicrobials effective against anaerobic and aerobic bacteria is an important component in the management of PA.
Recovery of anaerobes from the cores of tonsils of patients with recurrent GABHS tonsillitis
Using quantitative methods, Brook and Foote43 found similar polymicrobial aerobic and anaerobic bacterial flora in the cores of 4 normal tonsils as compared to 4 recurrently inflamed tonsils. The number of several species of organisms and the concentration of bacteria, however, was higher in children with recurrently inflamed tonsils (104 to 106 /gram) as compared to those with normal tonsils.(106 to 108 /gram) This was particularly true for encapsulated pigmented Prevotella and Porphyromonas spp. (previously called Bacteroides melaninogenicus group) isolates.
Several studies 7-11,28,44-47 determined the aerobic and anaerobic flora in the tonsillar core of children with recurrent tonsillitis. Because anaerobes are normal inhabitants of the oropharynx, as well as the surface of the tonsils, cultures taken directly from this area are difficult to interpret. To avoid this problem, specimens were obtained from the cores of surgically excised tonsils.
Reilly et al8 isolated anaerobic bacteria from all 41 tonsils; 76% of specimens yielded moderate to heavy growth and 80% contained more than one anaerobic species. This recovery rate fell to 56% after a 10-day course of metronidazole before tonsillectomy. A comparison was made between the flora of acutely inflamed tonsils and “healthy’ tonsils: over 90% of both groups yielded anaerobic bacteria, but they were present in significant numbers in 56% of cultures taken from acutely inflamed tonsils compared with 24% of cultures obtained from “healthy” children. P. melaninogenica was the most prevalent anaerobe, present in all of the specimens yielding anaerobic flora, and 60% of the isolates were in large numbers. Other GNAB were recovered from 7 of 16 specimens, and a single Fusobacterium spp. was recovered from five.
Brook, et al11 summarized microbiological studies of the core of tonsils removed from children with recurrent tonsillitis due to GABHS that were conducted during three periods, with 50 patients in each period: 1977-1978 (period 1), 1984-1985 (period 2), and 1992-1993 (period 3). (Tables 2,3)
Table 2. Predominate aerobic bacteria isolated from the core of excised tonsils from children during three periods. 11
| |||
No. of isolates (no. of BLPBs*) in indicated period
| |||
1977–1978
|
1984–1985
|
1992–1993
| |
Aerobic Organisms
|
(period 1)
|
(period 2)
|
(period 3)
|
Streptococcus pneumoniae
|
2
|
4
|
3
|
a-Hemolytic Streptococcus
|
41
|
38
|
34
|
g-Hemolytic Streptococcus
|
17
|
19
|
22
|
b-Hemolytic Streptococcus
| |||
Group A
|
11
|
8
|
10
|
Other
|
8
|
9
|
9
|
Staphylococcus aureus
|
24 (24)
|
21 (21)
|
23 (23)
|
Moraxella catarrhalis
|
25 (0)
|
22 (16†)
|
24 (20†)
|
Gram-positive bacilli
| |||
Haemophilus influenzae
| |||
Type b
|
12 (2)
|
38†‡ (21†‡)
|
6 (3)
|
Non–type b
|
2 (0)
|
5 (3)
|
32†§ (25†§)
|
Haemophilus parainfluenzae
|
5 (0)
|
4 (0)
|
6 (2)
|
Eikenella corrodens
|
4 (0)
|
6 (0)
|
5 (0)
|
Pseudomonas aeruginosa
|
1 (0)
|
0 (. . .)
|
1 (0)
|
Escherichia coli
|
1 (0)
|
2 (0)
|
2 (0)
|
Yeasts
| |||
Candida albicans
|
6
|
3
|
2
|
Total
|
185 (26)
|
195 (63||)
|
196 (74†)
|
NOTE. Tonsils from 50 children were studied during each period. Statistical analysis was conducted for all comparisons; significant results are identified by footnotes.
| |||
† P < .00l vs. 1977–1978.
‡ P < .001 vs. 1992–1993.
§ P < .001 vs. 1984–1985.
|| P < .005 vs. 1977–1978.
Table 3: Predominate Anaerobic bacteria isolated from the core of excised tonsils from children during three periods. 11
| |||
No. of isolates (no. of BLPBs*) in indicated period
| |||
1977–1978
|
1984–1985
|
1992–1993
| |
Organism
|
(period 1)
|
(period 2)
|
(period 3)
|
Peptostreptococcus species
|
34 (0)
|
44 (0)
|
45 (0)
|
Veillonella parvula
|
16 (0)
|
12 (0)
|
15 (0)
|
Eubacterium species
|
9 (0)
|
10 (0)
|
8 (0)
|
Propionibacterium acnes
|
2 (0)
|
3 (0)
|
2 (0)
|
Actinomyces species
|
2 (0)
|
2 (0)
|
1 (0)
|
Fusobacterium species
|
13 (0)
|
9 (3)
|
6 (4)
|
Fusobacterium nucleatum
|
26 (0)
|
33 (19†)
|
36 (32†)
|
Bacteroides species
|
18 (0)
|
15 (2)
|
12 (1)
|
Porphyromonas asaccharolytica
|
7 (1)
|
6 (5)
|
5 (3)
|
Prevotella melaninogenica
|
21 (7)
|
20 (15‡)
|
24 (20‡)
|
Prevotella intermedia
|
19 (7)
|
16 (12§)
|
15 (12§)
|
Prevotella oralis
|
12 (5)
|
14 (8)
|
12 (6)
|
Prevotella oris
|
5 (0)
|
7 (2)
|
3 (1)
|
Bacteroides fragilis group
|
12 (12)
|
17 (17)
|
10 (10)
|
Bacteroides ureolyticus
|
7 (0)
|
10 (0)
|
11 (3)
|
Total
|
207 (32)
|
218 (82†)
|
210 (93†)
|
NOTE. Tonsils from 50 children were studied during each period. Statistical analysis was conducted for all comparisons; significant results are identified by footnotes.
| |||
* b-Lactamase-producing bacteria.
† P < .001 vs. 1977–1978.
‡ P < .01 vs. 1977–1978.
§ P < .025 vs. 1977–1978.
Mixed flora were present in all tonsils, with 8.1 organisms per tonsil (3.8 aerobes and 4.3 anaerobes). The predominant isolates in each period were S. aureus, Moraxella catarrhalis, Peptostreptococcus, pigmented Prevotella and Porphyromonas., and Fusobacterium species. No change has occurred in the recovery of any of the bacterial species except for H. influenzae. The rate of recovery of H. influenzae type-b increased from 24% in period 1 to 76% in period 2 (P< .001); a decline to 12% in period 3 correlated with a concomitant increase in the frequency of recovery of non-type b strains of H. influenzae from 4% and 10% in periods 1 and 2, respectively, to 64% in period 3 (P < .001). Both the rate of recovery of BLPB and the number of these organisms per tonsil increased over time. Specifically, BLPB were detected in 37 tonsils (74%) during period 1, in 46 tonsils (92%) during period 2, and in 47 tonsils (94%) during period 3, and the number of such strains per tonsil increased from 1.1 in period 1 to 2.9 and 3.3 in periods 2 and 3, respectively. These findings indicate the polymicrobial aerobic and anaerobic nature of deep tonsillar flora in children with recurrent tonsillitis.
The recovery of polymicrobial aerobic-anaerobic flora in the tonsillar core including beta-lactamase-producing anaerobes was confirmed by Reilly et al8 who found penicillin resistance in 78% of the Bacteroides isolated from tonsils, Chagollan et al.,10 who isolated BLPB in 8 of 10 patients, and Tuner and Nord9 who recovered aerobic and anaerobic BLPB in 122 of 167 (73%) of their patients. ( Table 4 ) Prevotella oris-buccae accounted for 98 of 202 beta-lactamase-producing AGNB, recovered by Tunér and Nord9 who have also recovered F. nucleatum strains that produce beta-lactamase from infected tonsils. Kielmovitch et al48 recovered BLPB in all 25 patient, and Michelmore et al47, found these organisms in 82%.
Table 4. Microbiology of excised tonsils (268 patients)
Investigators
|
No. of patients
|
% BLPB
|
BLPB isolated
|
Reference
|
Brook, et al.
|
50
|
74
|
Pigmented Prevotella and Porphyromonas
|
7
|
B. fragilis
| ||||
S. aureus
| ||||
Reilly, et al.
|
41
|
78
|
Pigmented Prevotella and Porphyromonas
|
12
|
Tunér & Nord
|
167
|
73
|
P. oris-buccae
|
9
|
Pigmented Prevotella and Porphyromonas S. aureus
| ||||
Chagollan, et al.
|
10
|
80
|
S. aureus
|
10
|
P. oralis
| ||||
B. fragilis
| ||||
Kielmovitch et al.
|
25
|
100
|
Pigmented Prevotella & Porphyromonas
|
48
|
Mitchelmore et al.,
|
50
|
82
|
Pigmented Prevotella & Porphyromonas
|
47
|
Brook et al,
|
50
|
94
|
Pigmented Prevotella & Porphyromonas
|
11
|
BLPB = beta-lactamase-producing bacteria
| ||||
The microbiology of recurrent tonsillitis is different in children as compared to adults. The microbial flora of recurrently inflamed tonsils removed from 25 children with recurrent episodes of tonsillitis were compared with flora of tonsils removed from 23 adults suffering from similar illness.49 More bacterial isolates per tonsil were recovered in adults (10.2 per tonsil) than in children (8.4 per tonsil). The difference between these groups was related to a higher recovery rate in adults of pigmented Prevotella and Porphyromonas (1.6 / adult, 0.8 / child) and B. fragilis group (0.4 / adult, 0.2 / child) (Table 5). Conversely, GABHS were isolated in seven (28%) children as compared with their isolation in one (4%) adult. More isolates of BPLB per tonsil were recovered in adults. Forty-three BLPB were detected in 21 (91%) of the 23 tonsils removed from adults (1.9 / patient) as compared with 31 isolates in 16 (64%) of the 25 tonsils removed from children (1.2 / patient) (p = 0.04). The differences in the tonsillar flora may be associated with the effect of many more courses of antimicrobials given over the years to adults and the changes in tonsillar tissue that occur in this age group.
Table 5. Predominate organisms isolated in 48 excised tonsils from 25 children and 23 adults with recurrent tonsillitis* 49
| ||
No. of isolates
| ||
Children
|
Adults
| |
AEROBIC
| ||
S. pneumoniae
|
2
|
—
|
Group A beta-hemolytic streptococci
|
7
|
1
|
Group B beta-hemolytic streptococci
|
2
|
5
|
Group C beta-hemolytic streptococci
|
2
|
1
|
S. aureus
|
11 (11)
|
10 (10)
|
Moraxella catarrhalis
|
13 (2)
|
16 (3)
|
H. influenzae type B
|
6 (2)
|
4 (2)
|
H. parainfluenzae
|
3 (1)
|
1
|
Total
|
101 (16)
|
87 (15)
|
ANAEROBIC
| ||
Peptostreptococcus sp.
|
18
|
21
|
Fusobacterium sp.
|
20
|
24
|
Bacteroides sp.
|
15
|
13
|
Pigmented Prevotella and Porphyromonas sp.
|
21 (9)
|
37 (16)
|
Prevotella oralis
|
2 (1)
|
5 (2)
|
Prevotella. oris-buccae
|
3
|
4
|
B. fragilis group
|
5 (5)
|
10 (10)
|
B. ureolyticus
|
4
|
6
|
Total
|
110 (15)
|
148 (28)
|
* In parenthesis: number of organisms producing beta-lactamase.
| ||
Similar aerobic-anaerobic organisms were recovered in 22 young adults (mean age 23 years) who suffered from chronic tonsillitis.14 Mixed aerobic and anaerobic flora was obtained from core tonsillar cultures in all patients, yielding an average of 9.0 isolates (5.3 anaerobes and 3.7 aerobes) per specimen. The predominant anaerobic isolates were GNAB, Fusobacterium spp., and Gram-positive cocci. The predominant aerobic were alpha-hemolytic streptococci, S. aureus, M. catarrhalis, GABHS, and Haemophilus spp. Thirty two BLBP were recovered from 18 tonsils (82%). These included all eight isolates of S. aureus and five B. fragilis, and 11 of 24 pigmented Prevotella and Porphyromonas (46%). Because the known pathogen of tonsillitis, GABHS, was rarely recovered (only from 9% of patients), it is possible that other organisms, including anaerobes, have a pathogenic role in tonsillar infection and contribute to the inflammation.
These studies illustrate that anaerobic bacteria predominate in the cores of tonsils of children and adults with recurrent GABHS tonsillitis many cases without any aerobic bacteria.
Recovery of anaerobes from the cores of tonsils of patients with recurrent non-GABHS tonsillitis
We studied the microbiology of hypertrophic tonsils that developed following NST.12 The microbial flora of tonsils removed from 20 children who suffered from recurrent GABHS tonsillitis and 20 who had tonsillar hypertrophy, following recurrent NST, were evaluated. Similar polymicrobial aerobic-anaerobic flora were recovered from the cores of the tonsils in each group: an average of 9.4 isolates per tonsil (3.75 aerobic and 5.65 anaerobic) in the recurrent GABHS tonsillitis group and 8.8 isolates per tonsil (3.4 aerobic and 5.4 anaerobic) in the NST group.
Surgically excised tonsils
Surgically excised tonsils
BLPB were recovered more often in the recurrent GABHS tonsillitis group-32 isolates from 17 (85%) tonsils (1.6 / patient) as compared with 17 isolates from 8 (40%) tonsils from children with NST (0.85 / patient) (p < 0.005). These differences were mostly related to lower incidence of beta-lactamase-producing strains of M. catarrhalis and GNAB in hypertrophic tonsils following non-GABHS tonsillitis. Beta-lactamase-producing S. aureus were found with equal frequency in both groups. These findings demonstrate that although BLPB are recovered more often in recurrently inflamed tonsils following GABHS infection, they can be also found in hypertrophic tonsils following NST. Because many of the aerobic and anaerobic organisms are potential pathogens, they may play a role in the inflammatory process in NST.
Kuhn et al 50 performed quantitative aerobic and anaerobic cultures of tonsillar cores from children who had undergone elective tonsillectomy: 6 patients with recurrent tonsillitis (RT), 9 with recurrent tonsillitis with hypertrophy (RTH), and 8 with obstructive tonsillar hypertrophy (OTH). Mixed flora was present in all tonsils, yielding an average of 6.7 isolates. The highest recovery rate of organisms per tonsil was in patients with OTH (7.7 per tonsil), compared to 6.3 per tonsil in RT and 5.9 per tonsil in RTH. The predominant aerobic and facultative organisms were H influenzae (22 isolates), Neisseria spp. (16), S aureus (14), and Eikenella corrodens (14), and the predominant anaerobic bacteria were Fusobacterium spp. (8), Bacteroides spp. (7), and P. melaninogenica (5). The number of bacteria per gram of tonsillar tissue varied between 104 to 108. A higher concentration of S. aureus and H influenzae was found in hypertrophic tonsils (RTH and OTH) as compared to RT. These findings suggest the presence of an increased bacterial load in hypertrophic tonsils with and without inflammation (RTH and OTH). Further studies to elucidate the effect of selective antimicrobial therapy directed at these organisms may offer an alternative management of hypertrophic tonsils.
In a prospective, randomized, double-blind, placebo-controlled trial of 167 children Sclafani et al51 evaluated the short- and long-term effects of treatment of symptomatic chronic adenotonsillar hypertrophy with a 30-day course of amoxicillin-clavulanate. Patients were randomly treated with 30-day courses of either placebo (81 patients) or amoxicillin-clavulante (86 patients). The treatment group showed a significant reduction in the need for surgery in the short term compared with the placebo group at one month follow-up (37.5% vs 63%, respectively). The reduced need for surgery in the treatment group persisted at 3 months and 24 months compared with the placebo group (54.5% vs 85.7%, respectively, at 3 months; 83.3% vs 98.0%, respectively, at 24 months). The effect of amoxicillin-clavulante may be due to its efficacy against aerobic and anaerobic BLPB, including H influenzae and S aureus, that can be recovered in higher numbers in the cores of hypertropic tonsils compared with nonhypertropic tonsils.
Other anaerobes that may have a role in tonsillar infection are species of Actinomyces. Actinomycetes have been cultured on routine oral examination and are part of the normal oral flora. Mucosal disruption is required for the bacteria to become infective.52 The most common clinical presentation for the cervicofacial actinomycotic infection is a chronic, slowly progressive indurated mass, usually involving the submaxillary gland and frequently occurring after dental extraction or trauma.53 Several reports acknowledged the presence of actinomycetes in tonsil tissue.53
These studies illustrate that anaerobic bacteria predominate in the cores of tonsils of patients with recurrent NST and tonsillar hypertrophy and may respond to therapy directed against them.
Increased recovery rate of encapsulated pigmented Prevotella and Porphyromonas spp. in inflamed tonsils
Encapsulation is one of the virulence mechanisms of GNAB. Two studies support the importance of encapsulated anaerobic organisms in tonsillar and other respiratory infections.16,54 The presence of encapsulated and abscess-forming pigmented Prevotella and Porphyromonas was investigated in 25 children with acute tonsillitis and in 23 children without tonsillar inflammation (control).16
Encapsulated Gram negative anaerobe bacilli
Encapsulated pigmented Prevotella and Porphyromonas were found in 23 of 25 children with acute tonsillitis, compared to five of 23 controls (p > 0.0001). Subcutaneous inoculation into mice of the pigmented Prevotella and Porphyromonas strains that were isolated from patients with tonsillitis produced abscesses in 17 of 25 instances, compared with nine of 23 controls (p < 0.05). These findings suggest a possible pathogenic role for the pigmented Prevotella and Porphyromonas in acute tonsillar infection and indicate the importance of encapsulation in the pathogenesis of the infection.
In another study,54 the presence of encapsulated GNAB and anaerobic Gram-positive cocci was investigated in 182 patients with chronic orofacial infections, including 16 with peritonsillar abscesses and in the pharynx of 26 individuals without inflammation. One hundred-seventy of the 216 (79%) isolates of GNAB and anaerobic cocci were found to be encapsulated in patients with chronic infections, compared with only 34 of 96 (35%) controls (p < 0.001).
The recovery of a greater number of encapsulated anaerobic organisms in patients with acute and chronic orofacial infections provides further support for the potential pathogenic role of these organisms.
Synergy between anaerobes and GABHS
The potential for synergy between GABHS and 11 commonly associated aerobic and anaerobic microorganisms frequently isolated in tonsillar infections was evaluated in an animal model.55 Synergy was assessed by measuring the relative increase in colony-forming units (CFU) of GABHS and each of the 11 microorganisms inducing a subcutaneous abscess in mice. Of the 11 combinations of GABHS and aerobe or anaerobe, GABHS was enhanced in 10 cases. The other microorganisms that were also enhanced were S. aureus, H. influenzae type b, Klebsiella pneumoniae, P. melaninogenica and B. fragilis.
Synergistic relationship between aerobic and anaerobic bacteria
These findings confirm the mutual symbiotic enhancement of growth of GABHS in the presence of other aerobic and anaerobic bacteria. It is possible that such synergy exists also in patients with tonsillitis, where the same organisms are recovered in the tonsillar core.
The response to antibiotics effective against anaerobes in patients with infectious mononucleosis and non-GABHS tonsillitis
Several studies in which metronidazole was administered to patients with mononucleosis provided support of the role of anaerobes in tonsillitis.17,18 Metronidazole alleviated the clinical symptoms of tonsillar hypertrophy and shortened the duration of fever. Metronidazole has no antimicrobial activity against aerobic bacteria and is only effective against anaerobes. A possible mechanism of its action could be the suppression of the oral anaerobic flora that might have contributed to the inflammatory process induced by the Epstein-Barr virus.17,18 This explanation is supported by the increase recovery of P. intermedia and F. nucleatum during the acute phases of infectious mononucleosis.56
McDonald et al.19 demonstrated a reduction in the severity of symptoms of adults with NST following the administration of erythromycin. Merenstein and Rogers20 demonstrated definite improvement in the symptoms of patients with acute NST following penicillin therapy as compared with placebo. Putto21 showed an earlier reduction of fever following penicillin therapy of children with NST as compared with patients with viral tonsillitis. Brook22 demonstrated the efficacy of clindamycin over penicillin in the therapy of 40 patients with recurrent NST. From the second day following therapy on, significantly fewer patients who received clindamycin showed fever, pharyngeal infection, and sore throat. In one year following recurrent tonsillitis, infection was noted in 13 of the patients who received penicillin and in two patients who were treated with clindamycin (p < 0.001).
Brook & Gober57 evaluated the efficacy of antimicrobial therapy with metronidazole on the management of acute episodes ofNST . Forty children suffering from NST were included in the retrospective analysis, 20 were treated with metronidazole for 10 day, and 20 received no therapy. The efficacy of therapy was evaluated by the ability to alleviate the symptoms of acute infection. As compared with the untreated group, the group that received metronidazole, had a significant reduction in fever and sore throat one day after initiation of therapy, a significant reduction in the presence of fever, pharyngeal injection and sore throat within 2 days, and reduction in pharyngeal injection and tonsillar size at day 3. This study illustrated that metronidazole therapy was more efficacious than no therapy in relieving the signs and symptoms of acute episodes of NST . However, since this study was not designed as a randomized or double blind study, the conclusion that metronidazole therapy may be more efficacious than no therapy is not evidence based and should not change the treatment policies of NST . These findings should encourage further studies that are prospective and blinded that are needed to evaluate the use of antimicrobials effective against anaerobic bacteria in the treatment of NST .
Brook & Gober57 evaluated the efficacy of antimicrobial therapy with metronidazole on the management of acute episodes of
Effect of metronidazole on fever in children with non-streptococcal tonsillitis
The improvement in the clinical conditions of the patients with mononucleosis and NST supports the potential role of anaerobes in these forms of tonsillitis.
Immune response against anaerobes
A series of studies demonstrated an immune response 6‑7 week after the acute tonsillitis to F. nucleutum and P. intermedia in patients with tonsillar disease.23-26
The role of three oral flora organisms (Prevotella intermedia, Porphyromonas gingivalis, and Actinobacillus actinomycetemcomitans) was investigated in 31 children with recurrent NST.23 Antibody titers to the three organisms were measured by enzyme-linked immunosorbent assay in the 31 patients, as well as in 32 control patients who had not suffered from recurrent tonsillitis. None of the individuals in either group suffered from periodontal or dental illness. Significantly higher antibody levels to P intermedia were found in the study group as compared to controls (median 91.0 versus 72.5; p = .02). In contrast, the antibody titers to the other two organisms were generally low (less than 0.30), and no difference was found among the two study groups. The elevated antibody levels to P intermedia, a known oral pathogen that is also isolated from most recurrently inflamed tonsils, suggest a pathogenic role for this organism in recurrent tonsillitis.
The potential role of anaerobic bacteria in acute tonsillitis was investigated by determining the number of aerobic and anaerobic bacteria in the saliva of 20 children with acute GABHS pharyngo-tonsillitis, and 20 with acute NST, and by measuring the antibody titers to four GNAB that reside in the oropharynx (F. nucleatum, P. intermedia, P. gingivalis, and A. actinomycetemcomitans) in these and 20 control patients.26 (Table 6)
TABLE 6: Median (± SE) serum IgG antibody levels for four organisms as determined in 20 children with acute non-GABHS pharyngo-tonsillitis, 20 with acute GABHS pharyngo-tonsillitis and 20 controls. 26
Organisms
|
Non-GABHS
pharyngo-tonsillitis
|
GABHS
pharyngo-tonsillitis
|
Control
| ||
Day 1
|
Days 42-49
|
Day 1
|
Days 42-49
|
Day 1
| |
Fusobacterium nucleatum
|
46.5 (± 4.1)
|
131.6 (± 10.3)
|
47.1 (± 3.7)
|
116.8 (± 10.6)
|
43.2 (± 5.3)
|
Prevotella intermedia
|
51.5 (± 3.4)
|
136.4 (± 8.7)
|
49.7 (± 4.6)
|
101.0 (± 12.8)
|
48.3 (± 3.9)
|
Porphyromonas gingivalis
|
26.3 (± 2.5)
|
25.7 (± 4.1)
|
22.6 (± 4.5)
|
24.1 (± 5.2)
|
24.5 (± 4.1)
|
Actinobacillus actinomycetemcomitans
|
18.4 (± 2.1)
|
19.8 (± 3.0)
|
17.5 (± 1.8)
|
18.3 (± 2.6)
|
20.4 (± 2.8)
|
Serum antibodies to Prevotella in patients with recurrent non-streptococcal tonsillitis
An average of 8.8 aerobic and anaerobic isolates per patient saliva specimens were found during the acute tonsillitis stage in both groups, and 6.9 (in GABHS tonsillitis) and 5.6 (in NST) 5-6 weeks later. There were 10- to 1000-fold more bacteria in the acute stages of the inflammation in both GABHS and NST groups. These bacteria were S. aureus, H. influenzae, M. catarrhalis, Peptostreptococcus spp., F. nucleatum, Prevotella spp. and Porphyromonas spp. Significantly higher antibodies levels to F. nucleatum and P. intermedia were found in the second serum sample of patients with non-GABHS pharyngo-tonsillitis (P < 0.001) and GABHS tonsillitis (P < 0.05), as compared with their first sample or the levels of antibodies in controls. The increase in the number of several aerobic and anaerobic bacteria during acute tonsillitis and the increase in antibody levels to F. nucleatum and P. intermedia, known oral pathogens, may suggest a possible pathogenic role for these organisms in acute NST and GABHS tonsillitis.
The immune response to oral flora anaerobes was investigated in 22 patients with infectious mononucleosis,25 at day one and 42‑56 days later. Significantly higher antibody levels to F. nucleatum and P. intermedia were found in the second serum sample of patients as compared to their first sample. Significantly higher antibody levels to F. nucleatum and P. intermedia were found in the second serum sample of 17 patients with peritonsillar cellulitis or and 20 patients abscess, as compared to their first sample or the levels of antibodies in controls. 24
Antibodies to Fusobacterium and Prevotella in patients with peritonsillar abscess
Antibodies to Fusobacterium and Prevotella in patients with peritonsillar abscess
The increase in the number of several aerobic and anaerobic bacteria during acute tonsillitis and the increase in antibody levels to F. nucleatum and P. intermedia, known oral pathogens, may suggest a possible pathogenic role for these organisms in recurrent NST, peritonsillar cellulitis or abscess infection mononucleosis and acute NST and GABHS tonsillitis.
Conclusions
The data that supports the pathogenic potential of anaerobic in tonsillitis include the predominance of anaerobic bacteria in tonsillar and retropharyngeal abscesses, the core of tonsils of children with recurrent GABHS and NST, and the increased recovery rate of encapsulated pigmented Prevotella and Porphyromonas spp. in inflamed tonsils. Other finding that suggest this conclusion is the in- vivo synergy between anaerobes and GABHS, the response to antibiotics effective against anaerobes in patients with infectious mononucleosis and NST and the immune response against anaerobes in patients with NST and GABHS tonsillitis.
Although more studies are needed, these findings support the possible pathogenicity of GNAB in tonsillitis. Further studies are also needed to evaluate the use of antimicrobials effective against anaerobic bacteria in the treatment of NST.
REFERENCES
1. Brook, I., Grimm, S., Keibich, R.B.: Bacteriology of acute periapical abscess in children. J. Endodontics 7:378-80, 1981.
2. Brook, I.: Aerobic and anaerobic bacteriology of peritonsillar abscess in children. Acta. Pediatr. Scand. 70:831-8, 1981.
3. Brook, I.: Microbiology of retropharyngeal abscesses in children. Am. J. Dis. Child. 141:202-4, 1987.
4. Brook, I.: Aerobic and anaerobic bacteriology of cervical adenitis in children. Clin. Pediatr. 19:693-6, 1980.
5 Brook, I. , Finegold, S.M.: Bacteriology of chronic otitis media. JAMA 241:487-8, 1979.
6. Brook, I.: Aerobic and anaerobic bacteriology of chronic mastoiditis in children. Am. J. Dis. Child. 135:478, 1981.
7. Brook, I. , Yocum, P., Friedman, E.M.: Aerobic and anaerobic flora recovered from tonsils of children with recurrent tonsillitis. Ann. Otol. Rhinol. Laryngol. 90:261-3, 1981.
8. Reilly, S. Timmis P, Beeden AG, Willis AT.: Possible role of the anaerobe in tonsillitis. J. Clin. Pathol. 34:542-7, 1981.
9. Tunér, K., Nord, C.E.: Beta-lactamase-producing microorganisms in recurrent tonsillitis. Scand. J. Infec. Dis. 39(suppl.):83-5, 1983.
10. Chagollan, J.J., Ramirez, M.J., Gil, J.S.: Flora indigena de las amigdalas. Investigacion Medica Internacional 11:343-54, 1984.
12. Brook, I. , Yocum, P.: Comparison of the microbiology of Group A streptococcal and non-Group A streptococcal tonsillitis. Ann. Otol. Rhinol. Laryngol. 97:243-6, 1988.
15. Stammers, A.F.: Vincent's infection: observation and conclusions regarding the aetiology and treatment of 1017 civilian cases. Br. Dent. J. 76:147-52, 1944.
16. Brook, I. , Gober, A.E.: Bacteroides melaninogenicus: its recovery from tonsils of children with acute tonsillitis. Arch. Otolaryngol. 109:818-20, 1983.
17. Davidson, S., Kaplinsky C, Frand M, Rotem J. Treatment of infectious mononucleosis with metronidazole in the pediatric age group. Scand. J. Infect. Dis. 14:103-4, 1982.
18. Helstrom, S.A., Mandl, P.A., Ripa, T.: Treatment of anginose mononucleosis with metronidazole Scand. J. Infect. Dis. 10:7-9, 1978.
19. McDonald, C.J., Tierney, W.M., Hui, S.L.: A controlled trial of erythromycin in adults with non streptococcal pharyngitis. J. Infect. Dis. 152:1093-4, 1985.
20 Merenstein, J.H., Rogers, K.D.: Streptococcal pharyngitis: early treatment and management by nurse practitioners. JAMA 227:1278-82, 1974.
21. Putto, A.: Febrile exudative tonsillitis: viral or streptococcal. Pediatrics 80:6-12, 1987.
24. Brook I, Foote PA, Slots J. Immune response to Fusobacterium nucleatum and Prevotella intermedia in patients with peritonsillar cellulitis and abscess. Clin infect Dis. 20:S220–S221, 1995.
27. Wannamaker L.W. (1980) Bacterial interference and competition. Scand. J. Infect. Dis. Suppl. Suppl 24:82-85.
28. Brook, I. Gober, A. E.: Interference by aerobic and anaerobic bacteria in children with recurrent group A beta-hemolytic streptococcal tonsillitis. Arch. Otolaryngal. Head Neck Surg. 125: 225–554, 1999.
29. Finegold, S.M.: Anaerobic bacteria in human disease. New York, Academic Press. 1977.
30. Brook, I.: Microbiology of abscesses of the head and neck in children. Ann. Otol. Rhinol. Laryngol. 96:429-33, 1987.
31. Jokipii, A.M.M, Jokipii L., Sipila P., Jokinen K.: Semiquantitative culture results and pathogenic significance of obligate anaerobes in peritonsillar abscesses. J Clin Microbiol 26:957–61, 1988.
32. Floodstrom, A., Hallander, H.O.: Microbiological aspects of peritonsillar abscesses. Scand J Infect Dis 8:157–60, 1976.
33. Dodds, B., Maniglia, A.J.: Peritonsillar and neck abscesses in the pediatric age group. Laryngoscope 98:956–9,1988.
34. Hansen, A.: Nogle undersøgelser over gram-negative aerobe ikke-spore-dannende bacterier isolerede fra peritonsillere abscesser hos mennesker. Copenhagen, Ejnar Munksgaard, 1950.
35. Hallander, H.O., Floodstrom, A., Holmberg, K.: Influence of the collection and transport of specimens on the recovery of bacteria from peritonsillar abscesses. J. Clin. Microbiol. 2:504-9, 1975.
36. Sprinkel, P.M., Veltri, R.W., Kantor, L.M.: Abscesses of the head and neck. Laryngoscope 84:1143-8, 1974.
37. Lodenkämper, H., Stienen, G.: Importance and therapy of anaerobic infections. Antibiotic Medicine 1:653-9, 1955.
38. Baba, S., Mamiya, K., Suzuki, A.: Anaerobic bacteria isolated from otolaryngologic infections. Jpn. J. Clin. Pathol. 19 (suppl.):35-6, 1971.
39. Ophir, D., Bawnik J, Poria Y, Porat M, Marshak G.: Peritonsillar abscess. A prospective evaluation of outpatient management by needle aspiration. Arch. Otolaryngol. Head Neck Surg. 114:661-3, 1988.
40. Brook, I., Frazier, E.H., Thompson, D.H.: Aerobic and anaerobic microbiology of peritonsillar abscess. Laryngoscope 101:289–92, 1991.
41. Jousimies-Somer, H., Savolainen, S., Makitie, A., Ylikoski, J.: Bacteriologic findings in peritonsillar abscesses in young adults. Clin Infect Dis Suppl 4:S292–8, 1993.
42. Mitchelmore, I.J., Prior, A.J., Montgomery , P.Q.
43. Brook I, Foote PA Jr Microbiology of “normal” tonsils. Ann Otol Rhinol Laryngol. 99:980–3, 1990.
44. Rosen, G., Samuel, J., Vered, I.: Surface tonsillar microflora versus deep tonsillar microflora in recurrent tonsillitis. J. Laryngol. Otol. 91:911, 1977.
45. Veltri, R.W. Sprinkle PM, Keller SA, Chicklo JM. Ecological alternatives of oral microflora subsequent to tonsilectomy and adenoidectomy. J. Laryngol. Otol. 86:893-903, 1972.
46. Brook, I., Yocum, P., Shah, K.: Surface vs core-tonsillar aerobic and anaerobic flora in recurrent tonsillitis. JAMA 244:1696-8, 1980.
47. Mitchelmore IJ, Reilly PG, Hay AJ, Tabaqchali S.: Tonsil surface and core cultures in recurrent tonsillitis: prevalence of anaerobes and beta-lactamase producing organisms. Eur J Clin Microbiol Infect Dis. 13:542–8, 1994.
48. Kielmovitech IH, Keltel G, Bluestone C, et al.: Microbiology of obstructive tonsillar hypertrophy and recurrent tonsillitis. Arch Otolaryngol Head Neck Surg. 115:721–725, 1989.
50. Kuhn JJ, Brook I, Waters CL, Church LW, Bianchi DA, Thompson DH. Quantitative bacteriology of tonsils removed from children with tonsillitis hypertrophy and recurrent tonsillitis with and without hypertrophy. Ann Otol Rhinol Laryngol 104:646–52, 1995.
51. Sclafani AP, Ginsburg J, Shah MK, Dolisky JN: Treatment of symptomatic chronic adenotonsillar hypertrophy with amoxicillin/clavulanate potassium:short- and long-term results. Pediatrics. 101:675–681, 1998.
52. Bartlett, J.G., Gorbach, S.: Anaerobic infection of the head and nose. Otolaryngol. Clin. North Am. 9:655, 1976.
53. Pransky SM, Feldman JI, Kearns DB, Seid AB, Billman GF. Actinomycosis in abstructive tonsillar hypertrophy and recurrent tonsillitis. Arch Otolaryngol Head Neck Surg 117:883–5, 1991.
55. Brook I, Gillmore JD. Enhancement of growth of group A beta-hemolytic streptococci in mixed infections with aerobic and anaerobic bacteria. Clin Microbiol Infect.1:179-182, 1996.
