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Volume 6, Number 5—October 2000
Letter

Will Avilamycin Convert Ziracine into Zerocine?

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To the Editor: Avilamycin and evernimicin (Ziracine), which belong to the everninomicin class of drugs, are oligosaccharide antibiotics active against numerous gram-positive bacteria, including emerging pathogens such as glycopeptide-resistant enterococci, methicillin-resistant staphylococci, and penicillin-resistant pneumococci (1,2). The two drugs share the same mode of action--inhibition of translation--by binding to the same target in the large 50S ribosomal subunit (3). As a result, they also display cross-resistance: bacteria resistant to avilamycin are resistant to evernimicin (and vice versa), but not to other classes of drugs (4). Two mechanisms of resistance to this class of drugs are amino-acid substitution in ribosomal protein L16 (5) and mutations in the peptidyltransferase domain of 23S ribosomal RNA (6).

Avilamycin has been used in Europe for several years as a growth promoter for food animals, particularly pigs. Enterococci resistant to everninomycins have been isolated from animals receiving avilamycin as a food additive (4). Evernimicin is being evaluated as a human therapeutic agent. Indirect evidence indicates that the use as growth promoters of antibiotics that display cross-resistance with those used in human therapy contributes to antibiotic resistance in bacteria responsible for human infections (7). As early as 1969, a recommendation was published in the United Kingdom that antibiotics used to treat infections in humans not be used as animal food additives (8). In 1999, four antibiotics were banned as food additives in the European community.

Antibiotic resistance in human pathogens has become a major health issue, complicated by the fact that no new class of drugs has been introduced for human therapy in the last 25 years. Since the use of avilamycin in animals has favored selection of enterococcal strains that are cross-resistant to evernimicin (4), these bacteria can colonize the human gut or form a pool of resistance genes that can spread to human commensals or pathogens (9). The continued use of avilamycin as a growth promoter is likely to diminish the effectiveness of evernimicin if Ziracine or any member of the class is used for human therapy. Since everninomicins will be prescribed mainly for infections due to multiresistant gram-positive cocci, avilamycin should be prospectively banned as an animal growth promoter.

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Patrice Courvalin

Author affiliation: Institut Pasteur, Paris, France

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References

  1. Weinstein  MJ, Luedemann  GM, Oden  EM, Wagman  GH. Everninomicin, a new antibiotic complex from Micromonospora carbonacea. Antimicrob Agents Chemother. 1965;9:2432.PubMed
  2. Jones  RN, Barrett  MS. Antimicrobial activity of everninomicin (evernimicin), an oligosaccharide antimicrobial with a potent Gram-positive spectrum. Clin Microbiol Infect. 1995;1:3543. DOIPubMed
  3. McNicholas  PM, Najarian  DJ, Mann  PA, Hesk  D, Hare  RS, Shaw  KJ, Evernimicin binds exclusively to the 50S ribosomal subunit and inhibits translation in cell free systems derived from both gram-positive and gram-negative bacteria. Antimicrob Agents Chemother. 2000;44:11216. DOIPubMed
  4. Aarestrup  FM. Association between decreased susceptibility to a new antibiotic for treatment of human diseases, everninomicin (SCH 27899), and resistance to an antibiotic used for growth promotion in animals, avilamycin. Microb Drug Resist. 1998;4:13741. DOIPubMed
  5. Adrian  PV, Zhao  W, Black  TA, Shaw  KJ, Hare  RS, Klugman  KP. Mutations in ribosomal protein L16 conferring reduced susceptibility to evernimicin (SCH27899): implications for mechanism of action. Antimicrob Agents Chemother. 2000;44:7328. DOIPubMed
  6. Adrian  PV, Mendrick  C, Loebenberg  D, Shaw  KJ, Klugman  KP, Hare  RS, Ziracin (SCH27899) inhibits a novel ribosome target site: an analysis of 23S rRNA mutants. Abstract no. 845. Proceedings of the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. 1999; San Francisco.
  7. Wegener  HC, Aarestrup  FM, Jensen  LB, Hammerum  AM, Bager  F. Use of antimicrobial growth promoters in food animals and Enterococcus faecium resistance to therapeutic antimicrobial drugs in Europe. Emerg Infect Dis. 1999;5:32935. DOIPubMed
  8. Swann  MM. Report of the joint committee on the use of antibiotics in animal husbandry and veterinary medicine. London: Her Majesty's Stationery Office; 1969.
  9. Simonsen  GS, Haaheim  H, Dahl  KH, Kruse  H, Løvseth  A, Olsvik  Ø, Transmission of VanA-type vancomycin-resistant enterococci and vanA resistance elements between chicken and humans at avoparcin-exposed farms. Microb Drug Resist. 1998;4:3138. DOIPubMed

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Cite This Article

DOI: 10.3201/eid0605.000521

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Table of Contents – Volume 6, Number 5—October 2000

Page created: December 17, 2010
Page updated: December 17, 2010
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The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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