Reply to Cox et al.

    Foodborne and Diarrheal Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

    Repeating comments they had made previously [1, 2], Cox et al. [3] have provided a critique of our analysis of the FoodNet Campylobacter case-control study. Data from the FoodNet study, the largest reported case-comparison study of clinical outcomes of Campylobacter infections, demonstrated that resistance to fluoroquinolone (e.g., ciprofloxacin) is common in Campylobacter infections in humans and that persons with ciprofloxacin-resistant Campylobacter infection have a longer duration of diarrhea than do persons with ciprofloxacin-susceptible Campylobacter infection. Using standard epidemiologic principles, we found a consistent, strong, and robust association between having a longer mean duration of diarrhea and ciprofloxacin-resistant Campylobacter infection [4].

    When Cox et al. examined the FoodNet data, which were obtained under the Freedom of Information Act, they concluded that foreign travel confounded the association between resistance to ciprofloxacin and duration of diarrhea. Their analysis, which did not consider the effect of taking antidiarrheal medication, concluded that resistance to ciprofloxacin was not associated with an increased duration of diarrhea. In the analysis conducted by the Centers for Disease Control and Prevention, state health departments, the US Department of Agriculture, and the US Food and Drug Administration (FDA), we included foreign travel as a variable in the analysis and found that, when antidiarrheal medication is included in the model, the inclusion of foreign travel does not change the observed consistent association between resistance to ciprofloxacin and duration of diarrhea; foreign travel is not consistently or strongly associated with a longer duration of diarrhea, nor does it confound the observation that resistance to ciprofloxacin is associated with a longer duration of illness. As we noted in our article [4], taking antidiarrheal medication is associated with duration of diarrhea; failure to include the effect of antidiarrheal treatment leaves a major associated factor uncontrolled, producing spurious results.

    We do not agree with the supposition by Cox et al. that ciprofloxacin-resistant Campylobacter infections are less common now than they were during 1998. The incidence of laboratory-confirmed Campylobacter infection has declined in the United States in recent years, as indicated by FoodNet surveillance data [5], but the prevalence of Campylobacter resistance to ciprofloxacin has increased [6, 7]. When both the decline in the incidence of laboratory-confirmed Campylobacter infection and the increase in the prevalence of Campylobacter resistance to ciprofloxacin are taken into account, the incidence of ciprofloxacin-resistant Campylobacter infection increases an estimated 46%, from 1.4 infections/100,000 persons during 1997 to 2.0 infections/100,000 persons during 2001 [8].

    Readers interested in the legal context of this discussion, including the administrative law judge's initial decision to uphold the FDA's proposed prohibition of the use of fluoroquinolones in poultry, are referred to FDA docket number 00N-1571 [9].

    References

    1.  Department of Health and Human Services, US Food and Drug Administration. Written direct testimony of Louis Anthony Cox, Jr., Ph.D. Docket 00N-1571, exhibit B-1901. Available at: http://www.healthypoultry.com/doc_library/assets/B-1901_124.PDF. Accessed 12 October 2004. First citation in article

    2.  Kassenborg HD, Smith KE, Hoekstra RM, Carter MA, Tauxe RV, Angulo FJ. Reply to Cox. Clin Infect Dis 2004; 39:14001. First citation in article

    3.  Cox LA Jr, Copeland D, Vaughn M. Ciprofloxacin resistance does not affect duration of domestically acquired campylobacteriosis. J Infect Dis 2005; 191:15656 (in this issue). First citation in article

    4.  Nelson JM, Smith KE, Vugia DJ, et al. Prolonged diarrhea duration due to ciprofloxacin-resistant Campylobacter infection. J Infect Dis 2004; 190:11507. First citation in article

    5.  Foodborne Diseases Active Surveillance Network (FoodNet). FoodNet 2002 annual report. Atlanta, GA: National Center for Infectious Diseases. Available at: http://www.cdc.gov/foodnet/annual/2002/2002executive_summary.pdf. Accessed 13 October 2004. First citation in article

    6.  National Antimicrobial Resistance Monitoring System (NARMS). NARMS 2001 annual report. Atlanta, GA: National Center for Infectious Diseases. Available at: http://www.cdc.gov/narms/annual/2001/2001.pdf. Accessed 13 October 2004. First citation in article

    7.  Gupta A, Nelson JM, Barrett T, et al. Antimicrobial resistance among Campylobacter strains in the United States, 19972001: increasing prevalence of ciprofloxacin resistance. Emerg Infect Dis 2004; 10:11029. First citation in article

    8.  Nelson JM, Mlbak K, Theriot C, et al. Increasing incidence of ciprofloxacin-resistant Campylobacter infections in the United States: FoodNet and NARMS 19972001. Int J Med Microbiol 2003; 293(Suppl 35):46. First citation in article

    9.  Department of Health and Human Services, US Food and Drug Administration. Initial decision docket 00N-1571. Available at: http://www.fda.gov/ohrms/dockets/dailys/04/mar04/031604/00n-1571-idf0001-vol389.pdf. Accessed 14 March 2005. First citation in article