Quinolone Resistance in Campylobacter jejuni

Abstract & Commentary

Synopsis: Overall, quinolone resistance among isolates of Campylobacter jejuni from returned Finnish travelers increased during a 5-year period. The countries at highest risk for quinolone resistance are Thailand, India, and China. These findings indicate a need to reconsider the choice of antibiotics for self-treatment of traveler’s diarrhea in some countries.

Source: Hakanen A, et al. Emerg Infect Dis. 2003;9(2): 267-270.

A total of 354 Campylobacter jejuni isolates collected from travelers returning to Finland were evaluated for ciprofloxacin resistance. All subjects had traveled within 2 weeks of isolate collection. The specimens were collected from 1995 to 1997 and 1998 to 2000 by the laboratory staff of a hospital in Helsinki, who also determined minimal inhibitory concentrations (MICs) of ciprofloxacin and nalidixic acid for C jejuni isolates. Of these, 319 isolates were attributed to 40 specific countries of origin. Because of multiple destinations in the travel history, 22 isolates were attributed at the continent level, and the origins of 13 isolates were unknown.

Ciprofloxacin resistance in the C jejuni isolates was demonstrated in 49% of all isolates. Forty percent of the isolates collected from 1995-1997 were resistant compared with 60% obtained from 1998-2000. In a comparison by continent, Asia showed a significant increase in quinolone resistance from 45% to 72% between the two periods. There were very few isolates from North America; therefore, ciprofloxacin resistance for the two periods (0 and 67% respectively) may not be an accurate reflection of resistance. Although less dramatic, isolates from Africa and Europe also demonstrated increase in ciprofloxacin resistance.

There were 205 isolates collected from 1995-1997 and 149 isolates from 1998-2000. The most common countries of origin during the first period (1995-1997) for the C jejuni isolates were Spain (20%), India (9%), Thailand (8%), and Turkey( 8%). The most common countries of origin during the second period were Spain (25%), Thailand (22%), Portugal (4%), and Tunisia (4%). Hakanen and colleagues derived rate ratios for acquiring ciprofloxacin-resistant C jejuni from various destinations based on the number of trips to those destinations.

The rate ratios show that the risk of acquiring quinolone-resistant C jejuni is highest in Thailand, followed by India and China. The risk of acquiring ciprofloxacin-resistant C jejuni from Thailand appeared to be 10 times the rate in Spain or Portugal.

Comment by Lin H. Chen, MD

C jejuni is a motile, curved, Gram-negative rod, found worldwide and with numerous animal reservoirs. Human infections typically result from ingestion of contaminated water and food, in particular contaminated meat, but can also result from ingestions of unpasteurized milk.1 In developing countries, C jejuni is frequently isolated from asymptomatic persons, and it is a common cause of diarrhea in early childhood—especially those younger than 2 years old.2,3 An epidemiologic review following laboratory surveillance of Campylobacter in the United Kingdom indicated a high risk of campylobacteriosis in persons who had traveled to Indonesia (Bali), Singapore, the Philippines, followed by Thailand, Nepal, Sri Lanka, and Malaysia.4 Pakistan, Bangladesh, India, South America, and Africa also had greater risk than travel to other countries or domestic travel.

Clinical symptoms usually present after an incubation period of 2 days after exposure, although this ranges from 1 to 7 days.1 C jejuni may cause an enteritis or colitis affecting the jejunim, ileum, or colon. Acute symptoms can last up to 1 week, associated with fever, abdominal cramping, and stools ranging from loose to watery to frankly bloody. Symptoms are often self-limited. However, local spread can occur resulting in complications such as cholecystitis, pancreatitis, and peritonitis. C jejuni is one of the more common triggers of the Guillain-Barré syndrome. Organisms can be excreted for a mean of 16 days following convalescence.5

Treatment of C jejuni is primarily symptomatic and supportive, including hydration and replacement of electrolytes. Antibiotics are reserved for severe clinical presentations including high fever, bloody diarrhea, copious amounts of stool, or lack of response to conservative treatment. A number of antibiotics have been effective in the past, although erythromycin and ciprofloxacin have been drugs of choice.6 Antibiotic treatment does not prolong carriage, and erythromycin actually eliminates the organism from stool by 72 hours.7

Resistance among human isolates of C jejuni has previously been traced to the use of antibiotics in food animals.6 Unfortunately, quinolone resistance in C jejuni is now widespread, as encountered by Finnish travelers. The study demonstrates a significant increase in resistance during the 5-year period, and identifies countries associated with high risk for acquiring quinolone-resistant C jejuni: Thailand, India, and China. Because of its convenient dosing and good tolerance, azithromycin is already being recommended as a self-treatment for moderate cases of traveler’s diarrhea in travelers going to Thailand. The same recommendation may be applied to other countries as quinolone resistance emerges.

What other drugs are effective against C jejuni? Erythromycin (or another macrolide) is again the drug of choice, but resistance is also emerging. Aminoglycosides, chloramphenicol, clindamycin, nitrofurans, and imipenem should still be effective against C jejuni in severely ill patients.3

References

1. Blaser MJ, et al. JAMA. 1987;257:43-46.

2. Coker AO, et al. Emerg Infect Dis. 2002;8:237-243.

3. Allos BM. Clin Infect Dis. 2001;32:1201-1206.

4. The Campylobacter Sentinel Surveillance Scheme Collaborators. J Travel Med. 2003;10:136-138.

5. Wassenaar TM, Blaser MJ. Microbes Infect. 1999;1:1023-1033.

6. Engberg J, et al. Emerg Infect Dis. 2001;7:24-34.

7. Anders BJ, et al. Lancet. 1982;1:131-132.

Dr. Chen is Clinical Instructor, Harvard Medical School, Director, Travel Resource Center, Mt. Auburn Hospital, Cambridge, Mass.