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Studies including alpha-hemolytic streptococci

The scientists Eva Grahn Håkansson, Kristian Roos and Stig Holm and others have spent
many years studying the naturally occurring bacteria and their health benefits in the throat.
In several clinical trials they have shown that it is possible to decrease the risk of recurrence
of tonsillitis and otitis after antibiotic treatment by strengthening the normal flora in the
throat with natural alpha-hemolytic streptococci.
In 1983 Grahn et al investigated the interference between alpha-hemolytic streptococci and
different serotypes of group A streptococci (GAS) [1]. Out of 52 strains of alpha-hemolytic
streptococci, 4 strains with good pattern of inhibition were found. They also noticed that there
are strains of alpha-hemolytic streptococci only inhibiting a few serotypes of the group A
streptococci tested.

To investigate the role of the normal throat flora during an outbreak of streptococcal tonsillitis
(GAS), Grahn & Holm analyzed the throat flora of 45 persons in an apartment house area in
Umeå, Sweden [2]. Alpha-hemolytic streptococci with an interfering capacity on beta
streptococci were most frequently found in persons seemingly resistant to streptococcal
tonsillitis while patients with repeated tonsillitis often had beta streptococcal strains inhibiting
the growth of the persons own alpha-hemolytic streptococci. Table 1.

Table 1. Percentage of inhibiting alpha-hemolytic strains in non-infected and infected children, during spring
1980. [2].
a: Number of strains in brackets b: one child still infected Roos et al [3] recolonized patients with recurrent tonsillitis using alpha-hemolytic streptococci, to analyze the protective capacity of the new flora against recurrent streptococcal tonsillitis. 4 different strains of alpha-hemolytic streptococci were sprayed into the mouth of 9 persons, who together had experienced 36 episodes of acute tonsillitis during 3,5 months. During the 8 months of follow up, none of the patients experienced a new episode of tonsillitis. In a double blinded, randomized, placebo controlled study [4] 36 patients with recurrent streptococcal tonsillitis were enrolled. After antibiotic treatment, the patients were treated with a pool of 4 selected alpha-hemolytic streptococci (n=17) of placebo (n=19). No patient recurred during the first 2 months of follow-up in the active group, while 7 recurred in the placebo group. After 3 months 1 patient treated with alpha-hemolytic streptococci recurred, and 11 in the placebo group recurred (p=0.0009). Similar results were seen in another study by Roos [5], where 31 patients with recurrent streptococcal tonsillitis were included. After 10 days of antibiotic treatment, four selected alpha-hemolytic streptococci were sprayed into the mouth of the patients for 10 days. The follow-up period after the treatment was 3 months. None of the patients attracted a new tonsillitis during the follow up period, while 8 % in the control group (n=149) had asecond tonsillitis. Falck et al included 342 patients with clinical signs of tonsillitis in a randomized, placebo-controlled and double-blind, multicentre study [6]. The patients received antibiotics for 10 days, followed by 10 days of alpha-streptococcal of placebo spray treatment in the ratio of 2:1, giving 189 active patients and 93 placebo patients. Pharyngeal status, throat culture ans adverse events were investigated up to 75 days after treatment. The frequency of bacteriologically verified clinical recurrence was at last valid visit 19 % in the alpha-streptococcal group and 30 % in the placebo group, a statistically significant difference (p=0.037). Furthermore, at the last valid visit 5% of subjects in the alpha-streptococcal and 12% in the placebo group were healthy carriers, bacteriological treatment failures, of GAS (p=0.029). In another randomized, placebo-controlled, double-blind, multicentre study [7], 130 patients with recurrent tonsillitis were enrolled. The patients received antibiotic treatment for 10 days, followed by 10 days of alpha-streptococci (n=51) or placebo spray treatment (n=61). The clinical recurrence in the alpha-streptococci group were 2 % and 23 % respectively, in patients given spray for at least 5 days (p=0.004). Figure 1. n
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Figure 1. Recurrence of tonsillitis during a 2 months follow-up period after treatment with alpha-hemolytic
streptococci (p=0.004) [7].
In a study [8] Tano et al aimed to elucidate the inhibitory activity of the normal
nasopharyngeal flora against the three most common otitis media (OM) pathogens in healthy
children, children with secretory otitis media (SOM) and children with recurrent otitis media
(rAOM). Isolates of alpha-hemolytic streptococci (AHS) and OM pathogens were recovered
from the tubal orifice in each child. The samples were taken from 20 healthy children under
general anesthesia, from 19 children with SOM and 20 children with rAOM. The method used
to test the bacterial interference in vitro was a modified agar overlay method. The AHS
sampled from the tubal orifice of the healthy children were able to inhibit 92% of the S.
peumoniae isolates, 74% of the non-typable H. influenzae isolates and 89% of the M.
catarrhalis isolates. The corresponding figures for children with SOM and children with
rAOM were: 73% of the S. pneumoniae isolates, 58 and 54% of the non-typable H. influenzae
isolates and 86 and 89% of the M. catarrhalis isolates. The AHS from children with SOM and
children with rAOM were significantly less capable of inhibiting the S. peumoniae and the H. influenzae isolates (p<0.001). The results suggest that the inhibitory activity of the normal bacterial flora at the tubal orifice against pneumococci and H. influenzae may be reduced in children with SOM and rAOM. Roos et al [9] performed a double blind, randomised, placebo controlled study involving 130 children prone to otitis media. Children with no recurrences during the last month received phenoxymethylpenicillin (n = 22), and those with a recurrence within 1 month received amoxicillin clavulanic acid (n = 86), both twice daily for 10 days. These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days. At day 60 the same spray was started for another 10 days. Recurrence of otitis media during follow up and a normal tympanic membrane was measured at the last valid visit. At 3 months 22 children (42%) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 (22%) of those given placebo. This difference was shown separately for recurrences of both acute otitis media and secretory otitis media. Figure 2. n
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Figure 2. % healthy children with a normal tympanic membrane after treatment with alpha-hemolytic
streptococci (p=0.02) [9].

Skovbjerg performed a double blind, pilot/premlininary study, including 60 children with
long-standing SOM (median 6 months) who were scheduled for insertion of tympanostomy
tubes [10]. The children were randomized to nasal spray treatment with Streptococcus sanguis
89a, Lactobacillus rhamnosusLB21 or placebo for 10 days before surgery. Complete or
significant clinical recovery occurred in 7/19 patients treated with S.sanguis compared to 1/17
patient in the placebo group (p<0.05). In the L. rhamnosus treatment group 3/18 patients were
cured or much better (p=0.60 compared with placebo).
Referenser
1. Grahn, E., et al. Interference of alpha-hemolytic streptococci isolated from tonsillar surface on beta-hemolytic streptococci (streptococcus pyogenes) – a methodological
study. Zentralbl Bakteriol Mikrobiol Hyg A. 1983. 254(4): p. 459-68.
2. Grahn, E. and S.E. Holm. Bacterial interference in the throat flora during a streptococcal tonsillitis outbreak in an apartment house area. Zentralbl Bakteriol
Mikrobiol Hyg A. 1983. 256(1): p. 72-9.
3. Roos, K., et al. Treatment of recurrent streptococcal tonsillitis by recolonization with alpha-streptococci. Eur J Clin Microbiol Infect Dis. 1989. 8(4): p. 318-9.
4. Roos, K., et al. Alpha-Streptococci as supplementary treatment of recurrent streptococcal tonsillitis: a randomized, placebo controlled study. Scand J Infect Dis.
1993. 25: p. 31-35.
5. Roos, K., et al. Interfering alpha-streptococci as a protection against recurrent streptococcal tonsillitis in children. Int J Pediatr Otorhinolaryngol. 1993. 25(1-3): p.
141-8.
6. Falck, G., et al. Tolerance and efficacy of interfering alpha-streptococci in recurrence of streptococcal phryngotonsillitis: a placebo-controlled study. Acta Otolaryngol.
1999. 119(8): p. 944-8.
7. Roos, K., et al. Recolonization with selected alpha-streptococci for prophylaxis of recurrent streptococcal pharyngotonsillitis – a randomized placebo-controlled
multicentre study. Scand J Infect Dis. 1996. 28(5): p. 459-62.
8. Tano, K., et al. Inhibition of OM pathogens by alpha-hemolytic streptococci from healthy children, children with SOM and children with rAOM. Int J Pediatr
Otorhinolaryngol. 2000 Dec 22;56(3):185-90.
9. Roos, K., et al. Effect of recolonisation with “interfering” alpha-streptococci on recurrences of acute and secretory otitis media in children: randomised placebo
controlled trial. 2001. 27(322): p. 1-4.
10. Skovbjerg, S., et al. Spray bacteriotherapy decreases middle ear fluid in children with secretory otitis media. Arch Dis Child. 2009. 94(2): p. 92-8.

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