Abstract. Campylobacter is a leading cause of traveler's diarrhea in Thailand. Since resistance to quinolones is high among Campylobacter isolates, empiric therapy with quinolones for traveler's diarrhea may be ineffective in this region. We conducted an observational study among 169 U.S. military personnel with acute diarrhea and compared their microbiologic findings to those of 77 asymptomatic personnel deployed to Thailand in May 1998. Of 146 pathogenic bacterial isolates, the most common were nontyphoidal Salmonella (n ס 31), enterotoxigenic Escherichia coli (n ס 24), and C. jejuni/coli (n ס 23). Campylobacter was strongly associated with disease (odds ratio ס 5.9; 95% confidence interval ס 1.3−37.3), with a more severe clinical presentation, and with a reduced functional ability at presentation (P ס 0.02). In vitro resistance to ciprofloxacin was observed in 96% of the Campylobacter isolates. Sub-optimal treatment response to ciprofloxacin was observed in 17% of the cases of Campylobacter infection versus 6% due to other causes. These results highlight the importance of Campylobacter as a cause of severe traveler's diarrhea in Thailand and illustrates the ongoing problem with antibiotic-resistant strains and associated treatment problems.
To determine the efficacy of loperamide given with long- and short-course quinolone therapy for treating traveler's diarrhea, 142 US military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of ciprofloxacin twice daily with loperamide. Culture of pretreatment stool specimens revealed campylobacters (41%), salmonellae (18%), enterotoxigenic Escherichia coli (ETEC, 6%), and shigellae (4%). Of the participants, 87% completely recovered within 72 h of entry. Total duration of illness did not differ significantly among the three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group reported a lower cumulative number of liquid bowel movements at 48 and 72 h after enrollment compared with patients in the single-dose ciprofloxacin plus placebo group (1.8 vs. 3.6, P = .01; 2.0 vs. 3.9, P = .01). While not delivering a remarkable therapeutic advantage, loperamide appears to be safe for treatment of non-ETEC causes of traveler's diarrhea. Two of 54 patients with Campylobacter enteritis had a clinical relapse after treatment that was associated with development of ciprofloxacin resistance.
Chromosomal DNA fragments from a uropathogenic isolate of Proteus mirabilis were inserted into the cosmid vector pHC79 to construct a genomic library in Escherichia coli HB101. A urease-positive recombinant cosmid, designated pSKW1, was recovered. Sequential recombinant manipulation of pSKW1 yielded a 10.2-kilobase plasmid, designated pSKW4, which encoded three urease isozymes with electrophoretic mobilities identical to those of the donor P. mirabilis strain. Plasmid pSKW4 gene sequences encode seven proteins designated 68K (apparent molecular weight, of 68,000), 28K, 25K, 22.5K, 18.5K, 7.5K, and 5.2K within the limits of the urease gene complex. Insertion mutations in genes encoding the 68K, 28K, 25K, 22.5K, 7.5K, and 5.2K proteins resulted in complete or partial (22.5K) loss of urease activity. There was no reduction in urease activity when the gene encoding the 18.5K protein was inactivated.
Three groups of six monkeys (Aotus nancymae) each were inoculated intragastrically with increasing doses of Campylobacter jejuni. Infection resulted in fecal colonization (100% of monkeys), dose-related diarrhea, and robust immune responses. Colonization duration and diarrhea rate were reduced upon secondary challenge. A. nancymae may be useful for studying anti-Campylobacter vaccine efficacy.
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