Bacteriotherapy: The Time Has Come

[Guest guest]

BMJ 2001;323:353-354 ( 18 August )

Editorials

 

Bacteriotherapy: the time has come

Bacterial interference is an increasingly attractive approach to

prevention and therapy

 

 

 

The worldwide emergence of bacterial resistance to antibacterial

agents has produced a need for new methods of combating bacterial

infections. This need is forced on us by the long time lag in

developing new antibacterial agents. And even though new agents may

be in the pipeline, they will not solve all current resistance

problems. In addition, we also have to recognise that the use of

antibacterial agents not only selects resistant bacteria but also

disturbs normal human flora, which may itself further inhibit our

defence against infection. Bacteriotherapyusing harmless bacteria to

displace pathogenic organismsis an alternative and promising way of

combating infections.1

 

A recent paper in the BMJ by Roos et al showed how commensal

haemolytic streptococci were used to replace the normal

nasopharyngeal flora in children with recurrent otitis media.2 The

results were astonishing. After treatment, recurrences of otitis

media fell to half of those in the control group; at three months 42%

of children given streptococci in nasal spray were healthy compared

with 22% of the controls; and the need for new courses of

antibacterial treatment decreased. This study is not the first of its

kind from this group: Roos et al have also successfully used

haemolytic streptococci in preventing recurrent streptococcal

tonsillitis.3

 

This approach to treatment is not new.1 Bacterial interference was

once widely studied, and attempts to influence colonisation of

pathogenic bacteria with " harmless " bacteria were carried out some

decades ago. In human health bacteriotherapy was probably forgotten

because of the continuous development of new, more potent

antibacterial agents and because of fears about possible side

effects. Avirulent bacterial strains can, in principle, also cause

infections. Though otherwise effective, Staphylococcus spp 502A

caused minor skin lesions in a few individuals when it was introduced

into the skin flora to interfere with a virulent strain of S aureus.1

Nevertheless, bacteriotherapy has already long been used in

animalsfor example, to prevent salmonellosis in chickens.4

 

The results of Roos et al show also that antibiotic treatment itself

increases the risk of recurrent otitis media, and we know that

antibiotic treatment for any purpose increases the risk of urinary

tract infections in young women.5 Again, this increased risk is

probably caused by the antibiotics disturbing the balance of normal

genital and perianal flora.

 

Bacteriotherapy has also been used for other indications. Faeces or a

mixture of faecal bacterial strains have been used to treat recurrent

Clostridium difficile infection.6 Although the efficacy of this

treatment method still remains undecided because no randomised trials

have been performed, Saccharomyces bourlardii yeast was used for the

same indication in a randomised trial, with good results.7 Milk

containing Lactobacillus GG, given to children in day care centres,

seems to reduce the rate and severity of respiratory infections.8

Lactobacilli have been used in various clinical conditionsfor

example, for prophylaxis of antibiotic induced diarrhoea (decreasing

the diarrhoea rate to one third compared with placebo) but also in

promoting recovery from acute diarrhoea in children.9 Moreover, non-

pathogenic Escherichia coli have successfully been used to treat

ulcerative colitis.10

 

Why are strategies such as bacteriotherapy arousing more interest in

our attempts to combat antibacterial resistance? Although

restrictions on use of antibacterial drugs in hospitals are effective

in reducing bacterial resistance, the increasing number of

immunocompromised patients in hospitals nevertheless tends to

increase their use. And although we have shown that the reduction of

antibiotics used in the community can reduce bacterial resistance,11

this is a long row to hoe. Also, it may be that bacterial resistance

is still too remote a problem for most physicians, patients, decision

makers, and the medical industry to cause any concerted action in

reducing antibacterial consumption. We do not even know the total

consumption of antibacterial agents among humans in the European

Union.12

 

In addition to bacteriotherapy, other strategies to reduce infection

and bacterial resistance include improved hygiene measures,

especially in hospitals but also in day care centres, and new

bacterial vaccines.12 In the future, treatment opportunities may

include antibody treatment and bacteriophage therapy.

 

In the meantime bacteriotherapy seems to be a promising candidate for

the future treatment and prevention of respiratory tract and

gastrointestinal infections. Several questions remain open, however,

such as safety. The haemolytic streptococci chosen by Roos et al

were selected for their superior ability to inhibit the growth of

respiratory tract pathogens. Even if bacteriotherapy is safe for

individual patients, the possibility remains that large quantities of

active bacteria used clinically might change the human flora at

population level.

 

Indeed, we still know very little about the complex system of human

flora. There is an immediate need for basic research, and new

molecular techniques should help.13 This research is needed not only

to develop bacteriotherapy and other medical treatments but also to

better understand the role of human florafor example, in food

processing. Certainly the human microbiome will present plenty of

challenges to eager explorers over the next few years.

 

Pentti Huovinen, chief physician.

 

Antimicrobial Research Laboratory, National Public Health Institute,

20520 Turku, Finland

 

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1. Sanders WE, Sanders C. Modification of normal flora by

antibiotics: effects on individuals and the environment. In: Root RK,

Sande MA, eds. New dimensions in antimicrobial therapy: contemporary

issues in infectious diseases. New York: Churchill Livingstone,

1984:217-241.

2. Roos K, Grahn Håkansson E, Holm S. Effect of recolonisation

with " interfering " streptococci on recurrences of acute and

secretory otitis media in children; randomised placebo controlled

trial. BMJ 2001; 322: 210-212[Abstract/Free Full Text].

3. Roos K, Holm SE, Grahn-Håkansson E, Lagergren L. Recolonization

with selected alfa-streptococci for prophylaxis of recurrent

streptococcal pharyngotonsillitisa randomised placebo-controlled

multicentre study. Scand J Infect Dis 1996; 28: 459-462[Medline].

4. Nurmi E, Rantala M. New aspects of Salmonella infection in

broiler production. Nature 1973; 241: 210-211[CrossRef][Medline].

5. Smith HS, Hughes JP, Hooton TM, Roberts P, Scholes D, Stergachis

A, et al. Antecedent antimicrobial use increases the risk of

uncomplicated cystitis in young women. Clin Infect Dis 1997; 25: 63-68

[Medline].

6. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing

Clostridium difficile diarrhoea in six patients. Lancet 1989; i: 1156-

1160.

7. McFarland LV, Surawicz CM, Greenberg RN, Fekety R, Elmer GW,

Moyer KA, et al. A randomised placebo-controlled trial of

Saccharimyces boulardii in combination with standard antibiotics for

Clostridium difficile disease. JAMA 1994; 271: 1913-1918[Abstract].

8. Hatakka K, Savilahti E, Pönkä A, Meurman JH, Poussa T, Näse L, et

al. Effect of long term consumption of probiotic milk on infections

in children attending day care centres: double blind, randomised

trial. BMJ 2001; 322: 1327-1329[Abstract/Free Full Text].

9. Arvola T, Laiho K, Torkkeli S, Mykkänen H, Salminen S, Maunula L,

et al. Prophylactic Lactobacillus GG reduces antibiotic-associated

diarrhea in children with respiratory infections: a randomised study.

Pediatrics 1999; 104: e64[Abstract/Free Full Text].

10. Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon A. Non-

pathogenic Escherichia coli versus mesalazine for the treatment of

ulcerative colitis: a randomised trial. Lancet 1999; 354: 635-639

[CrossRef][Medline].

11. Seppälä H, Klaukka T, Vuopio-Varkila J, Muotiala A, Helenius H,

Lager K, et al. The effects of changes in the consumption of

macrolide antibiotics on erythromycin resistance in group A

streptococci in Finland. N Engl J Med 1997; 337: 441-446

[Abstract/Free Full Text].

12. Huovinen P, Cars O. Control of antimicrobial resistance: time

for action. BMJ 1998; 317: 613[Free Full Text].

13. Hooper L, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI.

Molecular analysis of commensal host-microbial relationship in the

intestine. Science 2001; 291: 881-884[Abstract/Free Full Text].

 

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© BMJ 2001

 

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Bacteriotherapy may be useful in treating bacterial vaginosis

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BMJ 2001 323: 1128. [Extract] [Full Text]

 

This article has been cited by other articles:

 

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