ANTIBIOTIC IN POULTRY FEED DISCONTINUED
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A ProMED-mail post
<http://www.promedmail.org>
[see also:
Antibiotic in poultry feed discontinued - Worldwide 19991221173228]
Date: Mon, 17 Jan 2000 09:01:11 -0200
From: Peter Collignon <peter.collignon@act.gov.au>
Recently, Roche Vitamins made a decision to no longer manufacture
avoparcin. This will eventually lead to its worldwide withdrawal.
Avoparcin is a glycopeptide antibiotic used in animals and very similar to
vancomycin. Vancomycin is a "last line" antibiotic that is used in humans
to treat infections such as methicillin-resistant _Staphylococcus aureus_
(MRSA) and _Enterococcus_ (in someone who is penicillin allergic with a
serious enterococcal infection there is usually no alternative other than
vancomycin).
The use of avoparcin has been linked with the development and spread of VRE
(vancomycin-resistant _Enterococcus_) by molecular and epidemiological
evidence especially from Europe where it was extensively used as a growth
promoter [in livestock]. The use of avoparcin was made illegal in the
European Union about 3 years ago based on this and other evidence (it was
never approved for use in the USA and Canada because of a carcinogenic
potential) [Items available on the US Food and Drug Administration website
<http://www.fda.gov> refer only to antibiotic resistance, not to
carcinogenicity. - Mod.ES].
In mid 1999 I wrote in the Medical Journal of Australia a review of the
evidence linking avoparcin use with VRE and the spread of VRE through the
food chain. The distributors of avoparcin (Roche Vitamins) did not agree
with many of the statements I made in that paper, and they have had a
letter published last week in the Medical Journal of Australia pointing out
their many objections to this article. Their three their main arguments
were that 1) the quantities of avoparcin used in Australia was lower than
stated, 2) that there is no molecular evidence for the transmission of VRE
from animals and that 3) vancomycin had been rejected as a therapeutic drug
in humans prior to avoparcin being first used in livestock in 1975.
A condensed version of my answer to these comments is given below. It is
very difficult to get accurate details on the amount of antibiotics used in
animals. In Australia the amounts were based on import data supplied to
the Federal government and supplied by the pharmaceutical companies
themselves. The only published figures available in Australia were that
125 278 kilos was used per year between 1991 and 1993. Roche now claims
that avoparcin had only a 10% potency. However even with their 10% potency
claim this still means that over 12 000 kilos were used per year which is
still greatly in excess to the 197 kilos of vancomycin used in humans per
year during that period of time. This however also brings up the important
issue of what is in the other 90%, if it is not active avoparcin. One group
in Canada has shown that in the impurities associated with antibiotics,
there are often antibiotic resistance genes. It needs to be pursued to see
whether the genes that encode for vancomycin resistance (vanA and vanB) may
be present in the associated impurities.
There is now very strong evidence that the complex vanA gene cluster that
encodes for vancomycin resistance is very similar in various strains of VRE
that are found both in humans and in animals. There is however only a
single nucleotide variation in a very conserved part of this cluster
(either a G or T substitution) between pigs and poultry. Humans however
carry VRE strains that can have both these variations. The most logical
conclusion from this finding is that man has acquired the strains
containing the vanA gene from both pigs and poultry.
Vancomycin was first developed and was given fast track approval in the USA
in the late 1950s because of the wide spread dissemination of penicillin
resistant Staphylococcus. aureus strains which followed the introduction
and widespread use of penicillin. Vancomycin use did decrease after
semi-synthetic penicillins became available and which were effective
against S. aureus (e.g. methicillin, oxacillin). However, because of the
development and widespread dissemination of MRSA strains in the late 1960s
and early 70s, vancomycin has continued to be used widely, particularly in
hospitals ever since its initial introduction. It is obviously, therefore,
incorrect to say that vancomycin was discarded as a useful drug in humans
at the time that avoparcin was used as a growth promoter in the 1970s in
animals.
VRE however does not only develop and spread because of the use of
avoparcin. Obviously the use (and overuse) of vancomycin in human medicine
has played a major contribution. However avoparcin (and other antibiotics
used as growth promoters) now only result in a few percent improvement in
animal weight gain (and in some studies no weight gain). It seems therefore
foolish to risk spreading a bacteriumsuch as VRE (with is often untreatable
with antibiotics) through the food chain for such little economic gain.
Avoparcin as most of you know is banned in Europe, the USA and Canada. I
think New Zealand is looking to ban it also. In Australia it was under
review by the NRA (The agriculture regulatory authority for this country)
but the review I understand has now been terminated because Roche have
decided to no longer manufacture avoparcin on a worldwide basis. It
remains unclear how many years of stock that Roche may still have and for
how many more years we may have avoparcin in Australia (and elsewhere in
the world) since there now appears to be no move by any Australian
government agency to ban it in this country. I am also not sure what
happens if Roche were to sell their licence/manufacturing process to
another company and it was then manufactured by someone else. Does anyone
know? Are there other glycopeptides that may be planned or already in use
in animals? Is vancomycin used in animals anywhere in the world?
Interested to get feedback on what others think.
****
References
1. Collignon P. Vancomycin-resistant enterococci and use of avoparcin in
animal feed: is there a link? Med J Aust Vol 172 3 January 2000 43/44.
2. Ian G Partridge. Vancomycin-resistant enterococci and use of avoparcin
in animal feed: is there a link? Med J Aust Vol 172 3 January 2000 43/44.
3. Jensen LB. Differences in the occurrence of two base pair variants of
Tn1546 from vancomycin-resistant enterococci from humans, pigs and poultry.
Antimicrob Agents Chemother 1998; 42: 2463-2464.
4. Turnidge J, Howard R. Australia's antibiotic burden. Aust Microbiol
1996; 17: 11.
5. Webb V, Davies J. Antibiotic preparations contain DNA: a source of drug
resistance genes? Antimicobiol Agents Chemother 1993; 37: 2379-2384.
6. Cooper G, Given D. Vancomycin: a comprehensive review of 30 years of
clinical experience. John Wiley and Sons Medical Group Company, 1986.
7. Collignon P. Antibiotics in animals: a resistance problem for man?
Microbiol Aust 1999; 20: 18-20.
-- Peter Collignon Clin A/Prof, Canberra Clinical School Infectious Diseases Physician and Microbiologist Canberra Hospital, Australia. ph 61 2 62442105; fax 61 2 62810349 e-mail: peter.collignon@act.gov.au[The letter of Ian Partridge cited above as reference (2) refers to Cyanimid sales reports to support claims of lower avoparcin usage in Australia, a 1996 report of an EU Scientific Committee for Animal Nutrition to support the authors point that there is no clear link between antibiotic usage for livestock growth promotion, presents an alternative interpretation of the work of Jensen et al. (reference 3 above), and cites the Heidelberg Appeal Netherlands Report of 1999 as concluding that the use of antibiotics as growth promoters has not compromised the human therapeutic use of related antibiotics. He also claims evidence of proven efficacy of avoparcin additives for prophylaxis of necrotic enteritis in poultry (no reference given). Readers are encouraged to review references (1) and (2) above in their entirety. - Mod.ES] .................................................jw/es -- Visit ProMED-mail's web site at <http://www.promedmail.org>. Send all items for posting to: promed@promedmail.org (NOT to an individual moderator). If you do not give your full name and affiliation, it may not be posted. Send commands to subscribe/unsubscribe, get archives, help, etc. to: majordomo@promedmail.org. For assistance from a human being send mail to: owner-promed@promedmail.org. ############################################################ ############################################################
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