Research Spotlight: In vivo development of antibiotic resistance in Campylobacter infection

By Matt Wargo • December 10th, 2010

Citation: J. C. Lindow, F. Poly, D. R. Tribble, P. Guerry, M. P. Carmolli, S. Baqar, C. K. Porter, K. K. Pierce, M. J. Darsley, K. S. Sadigh, E. A. Dill, the Campylobacter Study Team, and B. D. Kirkpatrick. 2010. Caught in the Act: In Vivo Development of Macrolide Resistance to Campylobacter jejuni Infection. J Clin Microbiol 48(8):3012–3015.

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Author’s association with MMG:
Janet Lindow- is a Research Associate in the Kirkpatrick lab
Beth Kirkpatrick- is an Associate Professor
M. Carmolli – Research Technician in the Kirkpatrick lab
K.S. Sadigh – former member of the Kirkpatrick lab and clinical team
E. Dill – Research Technician in the Kirkpatrick lab
Campy Team- members of the Kirkpatrick lab and clinical team

Significance:
Campylobacter jejuni is a leading cause of enteritis (inflammation of the small intestine) worldwide resulting in ~400 million cases annually. Little is known about the human immune response to C. jejuni infection including the immune correlates of protection and mechanisms of clearance from the human gut. In the healthy host many C. jejuni infections resolve without medical intervention; however, campylobacteriosis is associated with a surprising number of post-infectious sequelae. These include reactive arthritis and irritable bowel syndrome, as well as Guillan-Barré syndrome, which can lead to paralysis and even death. Antibiotic resistance in C. jejuni is also rapidly increasing, leaving children in the developing world and immunocompromised individuals with dwindling treatment options. Thus, understanding how the human immune system recognizes and responds to C. jejuni is important for developing effective vaccines and new antibiotics to treat C. jejuni infections.

Results:
We use an experimental human challenge model to better understand human immune responses to Campylobacter infections. Recently we identified the first case of in vivo-acquired antibiotic resistance causing an asymptomatic recrudescent infection in a healthy individual infected with Campylobacter jejuni during a clinical challenge study. The person mounted a normal immune response following infection with C. jejuni and was treated with appropriate antibiotics. The strain was shown to be identical to the C. jejuni challenge strain by PCR and pulsed field gel electrophoresis. However, the bacterial isolate from the recrudescent infection contained a single point mutation (A to G) at position 2075 in the 23S rDNA gene. This mutation is known to cause macrolide resistance in Campylobacter species. MIC testing confirmed that the isolate was resistant to macrolide antibiotics.

Conclusions:
Clinical Campylobacter model infection, which uses very closely monitored subjects dosed with C. jejuni, has brought to light the incidence of recrudescent infection in otherwise healthy adults. Our data suggest that following antibiotic treatment, microbiologic recrudescence can occur 14-28 days after the initial infection. Given the increasing Campylobacter resistance to fluoroquinolone antibiotics and the limited antibiotic treatment options for treating this infection, it will be important to monitor trends in resistance to the macrolide antibiotics. Although the development of in vivo macrolide resistance is likely under-recognized, our description of the development of in vivo resistance after appropriate use of antibiotics is a reminder of the principles of careful antibiotic stewardship.

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