To investigate the epidemiology of fluoroquinolone- resistant Campylobacter in the United States, we reviewed national surveillance data to determine the prevalence of antimicrobial resistance, particularly ciprofloxacin resistance, among Campylobacter isolates; conducted a case-control study to determine the propor- tion of ciprofloxacin-resistant infections that were domes- tically acquired; and performed a retail survey to determine the prevalence of ciprofloxacin-resistant Campylobacter contaminating chicken products sold in selected supermarkets. Methods National Surveillance for Resistance in Campylobacter 1989–1990 Sentinel County Study From 1989 to 1990, a national county-based survey of antimicrobial susceptibility among Campylobacter isolates was conducted. Sentinel clinical laboratories in 19 coun- ties participated. The methods of this survey are described elsewhere (19,20). Briefly, the first five sporadic Campylobacter isolates identified each month were for- warded to the Centers for Disease Control and Prevention (CDC). Patients with Campylobacter infection were inter- viewed with a standard questionnaire, which included information about clinical illness and exposures (i.e., food, animal, and foreign travel) during the 2 weeks before ill- ness onset. Isolates were determined to be Campylobacter by dark-field microscopic examination and hippurate hydrolysis (20–22). Hippurate-positive isolates were con- sidered C. jejuni. All isolates with questionnaires received during the first 4 months of the study underwent suscepti- bility testing. Because of a shortage of reagents, a random sample of 50% of isolates with completed questionnaires received during the last 8 months of the study was further characterized. Isolates were tested for susceptibility to azithromycin, chloramphenicol, ciprofloxacin, clin- damycin, erythromycin, gentamicin, nalidixic acid, and tetracycline by using broth microdilution methods (19). In 2003, a retrospective analysis of the hippurate-negative isolates was completed; these isolates were speciated by using methods described below. National Antimicrobial Resistance Monitoring System (NARMS), 1997–2001 NARMS for enteric bacteria is a collaboration between CDC, the Food and Drug Administration, and state and local health departments. The system monitors patterns of antimicrobial drug resistance. NARMS methods are described in detail elsewhere (23). In brief, isolates were tested for viability, confirmed as Campylobacter, and identified to the species level by using Antimicrobial-resistant Campylobacter the hippurate hydrolysis test according to published meth- ods (21,22). Hippurate-negative Campylobacter in which the hippuricase gene could be detected by polymerase chain reaction (PCR) were identified as C. jejuni (24). Isolates that tested negative for the hippuricase gene but positive for a C. coli-specific ceuE sequence were identi- fied as C. coli (25). Isolates that could not be identified as either C. jejuni or C. coli by these PCR assays were referred to the National Campylobacter Reference Laboratory at CDC for identification with genotypic (e.g., 16S rRNA sequencing) and phenotypic methods (21). Isolates were tested with the E-test system (AB BIODISK, Solna, Sweden) to determine MICs for six antimicrobial agents: chloramphenicol, ciprofloxacin, clin- damycin, erythromycin, nalidixic acid, and tetracycline. Beginning in 1998, azithromycin and gentamicin were also included. When available, National Committee for Clinical Laboratory Standards interpretive criteria for Enterobacteriaceae MICs were used; ciprofloxacin resist- ance was defined as MIC >4 µ g/mL, and erythromycin resistance was defined as MIC >8 µ g/mL (26). Multidrug resistance was defined as resistance to two or more of the original six antimicrobial agents. We used a multivariable logistic regression model to assess changes in the proportion of isolates with antimicro- bial drug resistance from 1997 through 2001 because the population under surveillance more than doubled from 1997 to 2001, and substantial site-to-site variation in prevalence of antimicrobial drug resistance was identified (i.e., uncertainty was found in the denominators for calcu- lating rates). The model was for antimicrobial drug resist- ance as a function of year and included main effects adjustments for age categories and site-to-site variation in prevalence. Within the available data, site by year interac- tion was not a significant factor but because the catchment areas expanded, the hypothesis of site by year interaction could not be fully tested. 1997 Retrospective Case-Comparison Study Using NARMS isolates, we conducted a retrospective case-comparison study in four NARMS sites (California, Connecticut, Georgia, and Oregon). Persons with ciprofloxacin-resistant (CipR) Campylobacter infection identified in 1997 were compared with persons in whom the diagnosis of ciprofloxacin-sensitive (CipS) Campylobacter infection was made that same year. We compared up to two CipS cases for each CipR case and matched cases by geographic site and date of stool speci- men collection. All case-patients were interviewed by tele- phone, usually within 8 weeks of their illness onset, about demographics, clinical information, and exposures (e.g., antimicrobial drug use in the 4 weeks before illness onset, foreign travel, and consumption of poultry and raw milk in Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 6, June 2004 1103