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Drug Resistance Looms in Traveler's Diarrhea


 

Major Finding: In Mexico, Guatemala, and India, the proportion of enterotoxigenic E. coli–resistant strains was 24% to levofloxacin, 20% to ciprofloxacin, 18% to azithromycin, 17% to rifaximin, and 5% to ceftriaxone.

Data Source: A study of stool samples from 434 travelers to India and Latin America.

Disclosures: Dr. Jeanette Ouyang-Latimer stated that she has no relevant conflicts of interest. The principal investigator, Dr. Herbert L. DuPont, has received speaking honoraria and/or research grants from several companies, including Salix Pharmaceuticals, Merck Vaccine Division, IOMAI, Intercell, Optimer Pharmaceuticals, and Santarus.

BETHESDA, MD. — The level of fluoroquinolone resistance in enteric pathogens has increased considerably over the last decade among travelers to Mexico, Guatemala, and India, based on an analysis of stool samples from more than 400 adult travelers to those countries.

But susceptibility has remained fairly stable for the poorly absorbed agent rifaximin as well as for azithromycin, suggesting that those agents may represent more suitable options for self-initiated treatment and prophylaxis of traveler's diarrhea, Dr. Jeanette Ouyang-Latimer said at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“It's important to monitor susceptibility patterns of enteropathogens causing traveler's diarrhea over time, especially when we've seen more liberal use of antibiotics for. The further increase in fluoroquinolone resistance may make it less ideal for those uses,” said Dr. Ouyang-Latimer of Baylor College of Medicine, Houston.

The stool samples were taken during 2006-2008 and were tested for enterotoxigenic Escherichia coli (ETEC), Salmonella, Vibrio, Shigella, Aeromonas, and Plesiomonas. The minimum inhibitory concentration (MIC) was determined by agar dilution for the antibiotics ampicillin; tetracyclines, including doxycycline, nalidixic acid, ceftriaxone, and trimethoprim-sulfamethoxazole (T/S); fluoroquinolones, including ciprofloxacin and levofloxacin; and azithromycin and rifaximin.

The most common agent was ETEC, with 270 samples isolated from 291 travelers to Mexico/Guatemala (grouped together as “Latin America”) and 98 of 143 travelers to India. Campylobacter was more common in samples from India than from Latin America (17 vs. 6).

From all the regions combined, the proportion of ETEC-resistant strains was 24% to levofloxacin, 20% to ciprofloxacin, 18% to azithromycin, 17% to rifaximin, and 5% to ceftriaxone. Resistance was much higher—around 50% each—to the older, less-used agents ampicillin, nalidixic acid, and T/S.

Contrary to previous reports from Southeast Asia, the campylobacter isolates did not show significant fluoroquinolone resistance, but 22% did show resistance to rifaximin, Dr. Ouyang-Latimer said.

By location, ETEC resistance to levofloxacin was far greater in India than in Latin America (41% vs. 20%). Azithromycin resistance also was higher in India than in Latin America (24.5% vs. 16%). All of the resistant campylobacter strains were seen in India, with 29% of the total showing rifaximin resistance.

The MIC at which 90% of the strains tested were inhibited (MIC90) from these samples was compared with MIC90 values previously reported from travelers to the same regions in 1997 (Antimicrob. Agents Chemother. 2001;45:212-6).

For ETEC, MIC90 levels had increased by twofold or greater for all the commonly used antibiotics. For ciprofloxacin, ETEC strains demonstrated a ninefold increase in resistance, from 3% in 1997 to 20% in 2006-2008. Levofloxacin resistance also increased dramatically among ETEC, from 3% to 24%.

These findings reflect the fact that fluoroquinolones and azithromycin often can be obtained without prescriptions in these regions, she noted. In contrast, ETEC retained 80% susceptibility to rifaximin and azithromycin. Ceftriaxone also showed low levels of resistance, but this agent is not practical to use for traveler's diarrhea, since it can only be given intramuscularly or intravenously. The MIC90 levels had also dropped for T/S, but it is not often used anymore.

For campylobacter, the MIC90 seems to have decreased, but the sample size for these isolates was small, she noted.

Although rifaximin and azithromycin do appear to remain good options for traveler's diarrhea, it's still not clear whether they can be used for such enteroinvasive pathogens as salmonella or shigella, she said.

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