Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 11, Number 6—June 2005

Antimicrobial Resistance in Campylobacter

On This Page
Article Metrics
citations of this article
EID Journal Metrics on Scopus

Cite This Article

To the Editor: Iovine and Blaser (1) write, "This therapeutic use [of enrofloxacin] was withdrawn (2) but is now under appeal" and "Despite the restrictions on enrofloxacin use, emergence of fluoroquinolone-resistant Campylobacter species, with poultry as an important source, has been documented in the United States… Therefore, our conclusion remains: use of enrofloxacin in poultry materially contributed to increase in human infection by fluoroquinolone-resistant Campylobacter species."

These claims propagate the following important errors. First, the therapeutic use of enrofloxacin was not withdrawn. Judge Davidson's order to withdraw the approval was an initial decision, to which exceptions were filed in 2004. A final decision rests with the US Food and Drug Administration Commissioner.

Second, poultry has not been identified as an important source of fluoroquinolone resistance in human Campylobacter isolates. The raw data of the cited Smith et al. article (3) indicate a nonsignificant negative association between chicken consumption and fluoroquinolone resistance in human isolates. Substantial resistance levels in Northern Hemisphere countries with and without enrofloxacin use, which occurred well before fluoroquinolones were ever used in animals (35), also suggest that attribution of such resistance to enrofloxacin is simplistic.

Finally, rational decision-making is based on probable future consequences of a decision, not past history or causes of the current situation. Iovine and Blaser's claim, "Thus the decision to withdraw therapeutic use of enrofloxacin (3) was warranted," is not implied, even if enrofloxacin use caused the emergence of fluoroquinolone resistance. If withdrawing enrofloxacin increases campylobacteriosis from airsacculitis-positive chickens, withdrawal may greatly harm human health. A rational withdrawal decision cannot be justified. In summary, Iovine and Blaser's view that enrofloxacin should be banned is not supported by the data that they have cited or by principles of sound risk management and decision-making.


Louis Anthony Cox*Comments to Author , Dennis Copeland†, and Michael Vaughn†
Author affiliations: *Cox Associates, Denver, Colorado, USA; †Bayer HealthCare, Shawnee, Kansas, USA



  1. Iovine  NM, Blaser  MJ. Antimicrobial resistance in Campylobacter. Emerg Infect Dis. 2004;10:1346.PubMedGoogle Scholar
  2. Vanhoof  R, Vanderlinden  MP, Dierickx  R, Lauwers  S, Yourassowsky  E, Butzler  JP. Susceptibility of Campylobacter fetus subsp. jejuni to twenty-nine antimicrobial agents. Antimicrob Agents Chemother. 1978;14:5536.PubMedGoogle Scholar
  3. Smith  KE, Besser  JM, Hedberg  CW, Leano  FT, Bender  JB, Wicklund  JH, Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992–1998. Investigation Team. N Engl J Med. 1999;340:152532. DOIPubMedGoogle Scholar
  4. Svedhem  A, Kaijser  B, Sjogren  E. Antimicrobial susceptibility of Campylobacter jejuni isolated from humans with diarrhea and from healthy chickens. J Antimicrob Chemother. 1981;7:3015. DOIPubMedGoogle Scholar
  5. Hollander  R. [In vitro activity of 23 chemotherapeutic agents against Campylobacter jejuni/coli strains isolated from feces]. Zentralbl Bakteriol Mikrobiol Hyg [A]. 1983;256:196201.PubMedGoogle Scholar


Cite This Article

DOI: 10.3201/eid1106.040689

Related Links


To the Editor: Cox and colleagues raised 3 major points. For the first point, we stated (1) "This therapeutic use was withdrawn but is now under appeal." The actual language of US Federal Drug Administration Judge Davidson's ruling is "Enrofloxacin found not shown to be safe under the conditions of use upon the basis of which the application was approved as required under § 512(e)(1)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) [21 U.S.C. § 360 b(e)(1)(B)]. Approval of NADA1 for enrofloxacin ordered withdrawn" (1). The drug manufacturer now is appealing the ruling.

For the second point, the authors state that poultry has not been identified as an important source of fluoroquinolone resistance in human Campylobacter isolates. In both Denmark and Spain, introduction of fluoroquinolones into poultry led to a rapid rise in resistance to Campylobacter in both poultry and human isolates (25), and banning their use in Denmark led to a rapid fall in resistance (6). Cox and colleagues may maintain that there is no "proof of a causal relationship," but the relationship is sufficiently strong, temporally restricted, biologically plausible, and coherent to convince disinterested observers, including Judge Davidson and ourselves, otherwise.

For the third point, that decisions must consider probable consequences, we agree. However, Cox et al. appear to use "possible" as their standard. In fact, nearly everything is possible, including the reasoning that they offer. However, in our opinion, based on experience as scientists and microbiologists, we deem the possible consequences described by Cox et al. as insubstantial compared to the clear and present danger to human health of continuing fluoroquinolone use in poultry. Obfuscation and delay have been effective tactics used to maintain profitability even when the facts indicate a different course of action. We hope that the FDA Commissioner will carefully weigh the actual evidence of the risk to human health imposed by the use of fluoroquinolones in poultry.

Martin J. Blaser, Department of Medicine, NYU School of Medicine, 550 First Ave, OBV-606, New York, NY 10016, USA; fax: 212-263-3969
Author affiliations: *New York University School of Medicine, New York, NY, USA; †New York Harbor Department of Veterans Affairs Medical Center, New York, NY, USA; 1New Animal Drug Application


  1. Daniel  J. Davidson FALJ. In: The matter of enrofloxacin for poultry: withdrawal of approval of Bayer Corporation's new animal drug application 1 (NADA) 140-828 (Baytril). In: FDA Docket No 00N-1571; 2004.
  2. Endtz  HP, Ruijs  GJ, van Klingeren  B, Jansen  WH, van der Reyden  T, Mouton  RP. Quinolone resistance in Campylobacter isolated from man and poultry following the introduction of fluoroquinolones in veterinary medicine. J Antimicrob Chemother. 1991;27:199208. DOIPubMedGoogle Scholar
  3. Reina  J, Borrell  N, Serra  A. Emergence of resistance to erythromycin and fluoroquinolones in thermotolerant Campylobacter strains isolated from feces 1987–1991. Eur J Clin Microbiol Infect Dis. 1992;11:11636. DOIPubMedGoogle Scholar
  4. Sanchez  R, Fernandez-Baca  V, Diaz  MD, Munoz  P, Rodriguez-Creixems  M, Bouza  E. Evolution of susceptibilities of Campylobacter spp. to quinolones and macrolides. Antimicrob Agents Chemother. 1994;38:187982.PubMedGoogle Scholar
  5. Velazquez  JB, Jimenez  A, Chomon  B, Villa  TG. Incidence and transmission of antibiotic resistance in Campylobacter jejuni and Campylobacter coli. J Antimicrob Chemother. 1995;35:1738. DOIPubMedGoogle Scholar
  6. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. Copenhagen: Danish Zoonosis Center, Danish Veterinary Institute; 2003.

Table of Contents – Volume 11, Number 6—June 2005

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Louis Anthony Cox, Jr., Cox Associates, 503 Franklin St, Denver, CO 80218, USA; fax: 303-388-0609

Martin J. Blaser, Department of Medicine, NYU School of Medicine, 550 First Ave, OBV-606, New York, NY 10016, USA; fax: 212-263-3969

Send To

10000 character(s) remaining.


Page created: April 24, 2012
Page updated: April 24, 2012
Page reviewed: April 24, 2012
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.