Risk Factors for Antimicrobial Resistance in Helicobacter pylori Table 2. Resistance of HARP isolates by regiona No. Amoxicillin, Tetracycline, Clarithromycin, Metronidazole, Region isolates no. (%) no. (%) no. (%) no. (%) Northeast 156 2 (1) 0 23 (15) 47 (30) South 92 1 (1) 0 13 (14) 13 (14) West 24 0 0 1 (4) 4 (17) Midwest 75 0 0 8 (11) 23 (31) Total 347 3 0 45 87 aN = 347; HARP, Helicobacter pylori Antimicrobial Resistance Monitoring Project. Resistant to 1 agent, no. (%) 54 (35) 19 (21) 3 (13) 25 (33) 101 Resistant to >1 agent, no. (%) 9 (6) 4 (4) 1 (4) 3 (4) 17 Resistant to >1 agent, no. (%) 63 (40) 23 (25) 4 (17) 28 (37) 118 Discussion The emergence of antimicrobial resistance in H. pylori represents a serious public health challenge because of the prevalence of infection and incidence of severe sequelae. A 12-fold increase in resistance to antimicrobial agents such as clarithromycin has been documented in cases in which antimicrobial therapy regimens do not eliminate H. pylori (9). Once resistance to clarithromycin appears, cross-resistance to all other macrolides also occurs, which eliminates the potential for their use in salvage therapies. In the past 5 years, amoxicillin and tetracycline resistance has also been described (6,10). H. pylori resistance is amply documented in a variety of study populations. However, most published studies have been based on cross-sectional designs, not prospective population-based surveillance of resistance. A meta-analy- sis of 20 nationwide clinical trials estimated H. pylori resistance to clarithromycin, metronidazole, and amoxi- cillin to be 10.1%, 36.9%, and 1.4%, respectively (6). These findings were also reflected in smaller single-site studies (11). Resistance rates may be higher in pediatric populations; for example, a study in Michigan demonstrat- ed that clarithromycin resistance in pediatric H. pylori strains was 2.5 times higher than that reported in adults in the same region and elsewhere in the United States (12). Single-site and multicenter surveillance network stud- ies in Britain, Croatia, the Czech Republic, Turkey, Table 3. Resistance of HARP H. pylori isolates by sitea Greece, Poland, Russia, Slovenia, Turkey, Estonia, Italy, Bulgaria, Germany, and Belgium have observed primary metronidazole and clarithromycin resistance with rates as high as 40.3% and 10.6%, respectively (13–17). A large prospective surveillance project in northeastern Germany showed primary metronidazole and clarithromycin resist- ance rates of 26.2% and 2.2%, respectively, in 1,644 clini- cal H. pylori isolates collected from 1995 to 2000 (17). High resistance rates to metronidazole and clarithromycin have been reported in Portugal, Brazil, Hong Kong, Saudia Arabia, and Lebanon (18–22). Overall, H. pylori resistance to metronidazole among single and multicenter surveil- lance networks is greater than all other resistant antimicro- bial agents combined. HARP is the only multicenter network providing ongo- ing prospective antimicrobial resistance and associated risk factor data for H. pylori in North America. The first 4 years of data show that resistance to antimicrobial drugs commonly used to treat H. pylori infections is widespread, though rates varied from year to year; this finding was true for both clarithromycin and metronidazole. We speculate that the precipitous decrease in metronidazole resistance in 2002 could be attributed to the reduction in isolates received by HARP, which limited the power and represen- tiveness of our sample. We performed a two-phased multivariate analysis on risk factors significantly associated with resistance on uni- No. Amoxicillin, Tetracycline Clarithromycin, Metronidazole, Location isolates no. (%) no. (%) no. (%) no. (%) Atlanta, GA 37 0 0 7 (19) 5 (14) Nashville, TN 45 1 (2) 0 5 (11) 5 (11) Galveston, TX 10 0 0 1 (10) 3 (30) Philadelphia, PA 41 1 (2) 0 6 (15) 15 (37) Washington, DC 93 1 (1) 0 15 (16) 31 (33) Indianapolis, IN 36 0 0 3 (8) 15 (42) Detroit, MI 18 0 0 3 (17) 4 (22) Cleveland, OH 6 0 0 0 1 (17) Milwaukee, WI 15 0 0 2 (13) 3 (20) Stanford, CA 24 0 0 1 (4) 4 (17) New York, NY 22 0 0 2 (9) 1 (5) aN = 347; HARP, Helicobacter pylori Antimicrobial Resistance Monitoring Project. Resistant to 1 agent, no. (%) 4 (11) 11 (24) 4 (40) 16 (39) 35 (38) 18 (50) 3 (17) 1 (17) 3 (20) 3 (13) 3 (14) Resistant to >1 agent, no. (%) 4 (11) 0 0 3 (7) 6 (7) 0 2 (11) 0 1 (7) 1 (4) 0 Resistant to >1 agent, no. (%) 8 (22) 11 (24) 4 (40) 19 (46) 41 (44) 18 (50) 5 (28) 1 (17) 4 (27) 4 (17) 3 (14) Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 6, June 2004 1091