Risk Factors for Antimicrobial Resistance in Helicobacter pylori network monitoring ongoing national and regional trends of antimicrobial resistance in H. pylori isolates in the United States. The network is positioned to document emerging resistance and to assist physicians in formulating therapy recommendations. We present the results of the antimicrobial resistance monitoring and risk factor analy- sis from data collected prospectively from 1998 through 2002. Materials and Methods During the course of the study, HARP consisted of 11 hospital study sites across the United States. The first five patients who sought treatment each month for esophago- gastro duodenal endoscopy (EGD) as part of treatment for H. pylori infection, confirmed by gastric biopsy, were enrolled at each site. When fewer than five eligible study participants were seen at a study center, those eligible were enrolled. Written, signed consent was obtained from all participants or their guardians. Culture of biopsied materi- al for H. pylori was performed at the study site or at the Atlanta Veterans Affairs Hospital. If primary isolation was performed at the HARP study site, isolates were placed in trypticase soy broth (TSB) supplemented with glycerol and stored at –70°C. Isolates were sent to the Centers for Disease Control and Prevention for antimicrobial resist- ance testing. Samples forwarded to the Atlanta Veterans Affairs Hospital for isolation were packed in 6 pounds of dry ice and maintained at –70°C to –80°C until cultured (up to 1 month). Each specimen was accompanied by a standard case report form containing 145 variables of demographic, clinical, and epidemiologic information. Laboratory Procedures Isolates were cultured on heart infusion agar (HIA) with 5% rabbit blood at 37°C in a microaerobic atmos- phere (10% CO2, 85% N2, 5% O2) for a minimum of 72 hours or until appearance of H. pylori colonies. Gastric biopsy specimens were homogenized by using a micropes- tle in a microcentrifuge tube, and the homogenates were added to HIA with 5% rabbit’s blood and Skirrow media and incubated at 37°C microaerobically for up to 2 weeks. Presumptive H. pylori colonies were subcultured for fur- ther testing. Isolates were confirmed as H. pylori if they demonstrated typical morphologic features by dark-field microscopy and if urease, oxidase, and catalase activities were detected. Also, a polymerase chain reaction amplifi- cation assay that used primers targeted at the ureA gene provided confirmation (7). Antimicrobial susceptibility testing was performed by the agar dilution method in accordance with National Committee for Clinical Laboratory Standards (NCCLS) protocols, except that defibrinated rabbit blood was used instead of aged sheep blood (8). For antimicrobial agents without an NCCLS- recommended breakpoint, breakpoints were selected after a review of the literature. Data Collection and Analysis Case report forms and laboratory data were entered into a MS Access 2000 database and analyzed by using SAS, version 8.2 (SAS Institute, Cary, NC). We defined a resistant case to be an HARP isolate that demonstrated any detectable resistance to metronidazole, clar- ithromycin, tetracycline, or amoxicillin. HARP study sites were assigned to the following four regions: Northeast (Washington, DC; New York, NY; and Philadelphia, PA), South (Atlanta, GA; Nashville, TN; and Galveston, TX), Midwest (Detroit, MI; Cleveland, OH; Indianapolis, IN; and Milwaukee, WI), and West (Palo Alto, CA). Differences between patients infected with resistant and susceptible strains of H. pylori were assessed by using the Fisher exact test, Mantel-Haenszel chi-square, or Student t test, as appropriate. A one-way analysis of variance (ANOVA) was used to determine antimicrobial resistance rate trends for clarithromycin and metronidazole. When the difference in the number of study participants that har- bored a resistant H. pylori infection and those who did not for a given risk factor was <2, we chose to exclude the risk factor from further analysis because of the possibility of arriving at a spurious association caused by small cell-size variations. This method enhanced the statistical reliability of all possible exposure and resistance associations con- sidered for multivariate modeling. Risk factors that met these criteria were subjected to a chi-square score model selection procedure to obtain the most significant and sta- ble multivariate model. Multivariate analyses were per- formed by using logistic regression to assess the independent association of identified risk factors with any detectable antimicrobial resistance using two different models. The first logistic regression model assessed significant univariate risk factors for antimicrobial resistance. A sec- ond logistic regression model was created that we condi- tioned on geographic location of HARP site, previous antimicrobial treatment for H. pylori infection, and antacid use to resolve colinearity issues with race. Results Of 317 enrolled HARP study participants for whom complete demographic information was available, 205 (65%) were male, 116 (37%) were white, 172 (54%) were black, 14 (4%) were Asian, 3 (1%) were Native American, and 12 (4%) were of other ethnic backgrounds. The medi- an age was 57 years (range 3–94 years). Among males, 97 (31%) were white, 90 (28%) were black, and 9 (3%) were Asian, 1 (0.3%) was Native American, and 8 (3%) were of other ethnic backgrounds. Among females, 19 (6%) were Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 6, June 2004 1089