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Letter
Enrofloxacin in Poultry and
Human Health
To the Editor: Following logic similar to that recently used by
the US Food and Drug Administration to withdraw approval for enrofloxacin,
a recent letter estimated that fluoroquinolone use in poultry could compromise
responses to antimicrobial drugs in >24,000 persons per year in the
United States (1). However, >99.9% of this
estimated risk appears to result from incorrect assumptions. Potentially
important corrections include the following: 1) not attributing resistance
from foreign travel and human ciprofloxacin use to domestic use of enrofloxacin
in poultry (this could reduce the estimated risk by ≈1/3) (2);
2) updating the estimated fraction of human foodborne Campylobacter
infections caused by poultry to reflect declines in microbial loads on
chicken carcasses since 1992 reduces the estimated risk by a factor of
perhaps 1/10 (3) (the cited 90% estimate by Hurd
et al. [1] was intended for use as part of a
conservative upper-bounding analysis, not as a realistic point estimate);
3) replacing an assumption that 10% of infected persons would benefit
from antimicrobial drug therapy with a more data-based value of 0.6% (4)
would reduce the estimated risk by a factor of 0.6/10 = 0.06; 4) replacing
an assumption that fluoroquinolones are prescribed for all affected
patients receiving antimicrobial drug treatment (rather than, for example,
erythromycin) by a more realistic value of fluoroquinolones being prescribed
for perhaps ≈50% of patients (2) reduces
the estimated risk by a factor of ≈50%; 5) replacing an assumption
that all such cases lead to compromised responses with a more data-driven
estimate that perhaps ≈17% of patients have compromised responses
would reduce the estimated risk by a factor of 1/6 (5);
and 6) recognizing that reducing enrofloxacin use may not decrease fluoroquinolone
resistance in all Campylobacter spp. from food animals (effect
not quantified) (6). Together, such changes reduce
the estimated risk by a factor of at least (1/3) × (1/10) ×
(0.6/10) × (1/2) × (1/6) = 0.00017, or by >99.9%.
More notably, the calculation in (1) also wrongly
assumes that the fraction of patients with fluoroquinolone-resistant infections
times the fraction of infections caused by poultry gives the fraction
of patients with compromised response caused by fluoroquinolone use in
poultry. As a simple counterexample, suppose that 80% of all infections
were caused by poultry, with the rest caused by something else (e.g.,
water), and that all and only the 20% of infections caused by the latter
source are resistant. Then the procedure in (1)
would estimate (80% of infections caused by poultry) × (20% of infections
resistant) = 16% as the fraction of resistant infections caused by poultry,
even though the correct answer is zero. Thus, the basic logic of the calculation
is flawed.
Louis Anthony Cox, Jr*†
*Cox Associates, Denver, Colorado, USA; and †University of Colorado Health
Sciences Center, Denver, Colorado, USA
Suggested citation
for this article:
Cox LA. Enrofloxacin in poultry and human health [letter]. Emerg Infect
Dis [serial on the Internet]. 2006 May [date cited]. Available
from http://www.cdc.gov/ncidod/EID/vol12no05/05-1477_06-0305.htm
References
- Collignon P. Fluoroquinolone
use in food animals [letter]. Emerg Infect Dis. 2005;11:1789–80.
- Cox LA Jr. Quantitative health risk analysis methods: modeling the
human health impacts of antibiotics used in food animals. New York:
Springer; 2005.
- Stern NJ, Robach MC. Enumeration
of Campylobacter spp. in broiler feces and in corresponding processed
carcasses. J Food Prot. 2003;66:1557–63.
- Busby JC, Roberts CT, Lin J, MacDonald JM. Bacterial foodborne disease:
medical costs and productivity losses. 1996 [cited 2006 Mar 22]. Washington:
US Dept of Agriculture, Economic Research Service. Agricultural economics
report 741. Available from http://www.ers.usda.gov/publications/aer741/
- Sanders JW, Isenbarger DW, Walz SE, Pang LW, Scott DA, Tamminga C,
et al. An
observational clinic-based study of diarrheal illness in deployed United
States military personnel in Thailand: presentation and outcome of Campylobacter
infection. Am J Trop Med Hyg. 2002;67:533–8.
- DANMAP—Use of antimicrobial agents and occurrence of antimicrobial
resistance in bacteria from food animals, foods and humans in Denmark.
2005 Jul [cited 2006 Mar 22]. Available from http://www.dfvf.dk/Files/Filer/Zoonosecentret/Publikationer/Danmap/Danmap_2004.pdf
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In response: Cox's letter (1)
contains a number of false assumptions, errors, misleading assertions,
and misquotations. Cox asserts that annually 1 person or fewer in the
United States will experience an adverse effect because of fluoroquinolone
use in poultry. He reduces 10-fold my referenced risk for persons acquiring
Campylobacter infections from poultry (2).
His unrealistically low estimate is not given in his referenced citation.
His estimated risk is also much lower than in the reference 2, which Cox
himself quotes, "Poultry is the most common cause of sporadic cases
of campylobacteriosis in the United States" (Economic Research Service
of the US Department of Agriculture) (3). Cox
knows that his assertion (4) that poultry make
little or no contribution to human Campylobacter infections has
been extensively examined and found to be wrong. Indeed, an entire section
in a recent US Food and Drug Administration (FDA) determination was written
about the unreliability of Cox's testimony and these assertions, a finding
made by both the FDA commissioner and an administrative law judge (5,6).
Cox also misquotes Busby et al. (3) when he
asserts that only 0.6% of persons with Campylobacter infections
benefit from antimicrobial drugs. The Busby article states that 0.6% of
persons with Campylobacter infections need "hospitalization,"
not how many would benefit from antimicrobial drug therapy. Cox has thus
made a misleading attribution (something he has previously been found
to do [5]).
Busby et al. (3) estimated that in 1993, ≈1,500,000
persons in the United States acquired Campylobacter infections
from food sources. Even if the proportion who can benefit from receiving
antimicrobial drugs is as low as 2%, this translates to 30,000 persons.
If 20% of these infections were caused by fluoroquinolone-resistant Campylobacter
spp., then 6,000 persons would potentially have their therapy and outcome
compromised, rather than the 1 person that Cox would have us believe.
More realistic is the figure of 24,000 persons estimated previously to
be at risk of having an adverse outcome (or ≈285 persons for every
1 million chickens treated with fluoroquinolones) (1).
Cox's assumptions and calculations thus seem flawed and unrealistic.
Peter Collignon*
*The Canberra Hospital, Woden, Australian Capital Territory, Australia
Suggested citation
for this article:
Collignon P. Enrofloxacin in poultry and human health [response]. Emerg
Infect Dis [serial on the Internet]. 2006 May [date cited]. Available
from http://www.cdc.gov/ncidod/EID/vol12no05/05-1477_06-0305.htm
References
- Cox LA. Enrofloxacin in poultry and human health
[letter]. Emerg Infect Dis. 2006;12:872–3.
- Collignon P. Fluoroquinolone
use in food animals [letter]. Emerg Infect Dis. 2005;11:1789–80.
- Busby JC, Roberts T, Jordan Lin C-T, MacDonald JC. Bacterial food-borne
disease: medical costs and productivity losses. [cited 2006 Mar 8].
Agricultural Economics Report No. (AER741). Washington: United States
Department of Agriculture; 1996. Available from http://www.ers.usda.gov/publications/aer741/
- Phillips I, Casewell M, Cox T, DeGroot B, Friis C, Jones RN, et al.
Does
the use of antibiotics in food animals pose a risk to human health?
A critical review of published data. J Antimicrob Chemother. 2004;53;28–52.
- US Food and Drug Administration. Final decision of the commissioner.
Proposal to withdraw the approval of the new animal drug application
for enrofloxacin for poultry [cited 2006 Mar 8]. Docket no. 2000N-1571.
p. 16–7; 108–19. Available from http://www.fda.gov/oc/antimicrobial/baytril.pdf
- US Food and Drug Administration. Initial decision. Withdrawal of approval
of the new animal drug application for enrofloxacin for poultry [cited
2006 Mar 8]. Docket no. 00N-1571. p. 13–5. Available from http://www.fda.gov/ohrms/dockets/dailys/04/mar04/031604/00n-1571-idf0001-vol389.pdf
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