J Microbiol Immunol Infect. 2017 Feb;50(1):75-82.

Antimicrobial resistance in Campylobacter coli and Campylobacter jejuni in cynomolgus monkeys (Macaca fascicularis) and eradication regimens

Tetsufumi Koga 1*, Wataru Aoki 2, Takashi Mizuno 2, Kuniko Wakazono 2, Junki Ohno 2, Tsunehiro Nakai 2, Takao Nomiya 2, Miki Fujii 2, Keiichi Fusegawa 1, Kazuya Kinoshita 1, Takakazu Hamada 1, Yoshinori Ikeda 2

1. Biological Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan

2. KAC Co., Ltd., Tokyo, Japan

*E-mail: koga.tetsufumi.zj@daiichisankyo.co.jp



Tetsufumi Koga, D.V.M., Ph.D.

Senior Scientist

Laboratory Animal Care & Management Group

Research Function



Background: Campylobacter spp. are zoonotic pathogens, however, knowledge about their presence and antimicrobial resistance in nonhuman primates is limited. Our animal facility purchased cynomolgus monkeys (Macaca fascicularis) from various Asian countries: China, Cambodia, Indonesia, the Philippines, and Vietnam.

Methods: Colonization by Campylobacter spp. was investigated in 238 of the monkeys from 2009 to 2012 and antimicrobial susceptibility testing was carried out for these isolates. Furthermore, we eradicated these pathogens from these monkeys.

Results: Campylobacter spp. were isolated from 47 monkeys from three specific countries: China, Cambodia, and Indonesia, with respective isolation rates of 15%, 36%, and 67%. Two monkeys, which were each infected with Campylobacter jejuni and Campylobacter coli, showed clinical symptoms of diarrhea and bloody feces. In total, 41 isolates of C. coli and 17 isolates of C. jejuni were detected. Antimicrobial susceptibility varied: in the monkeys from China, erythromycin (ERY)-, tetracycline (TET)-, and ciprofloxacin-resistant C. coli, in the monkeys from Cambodia, amoxicillin-intermediate, TET- and ciprofloxacin-resistant C. coli and amoxicillin- and ciprofloxacin-resistant C. jejuni, and in the monkeys from Indonesia, ciprofloxacin-resistant C. coli and TET- and ciprofloxacin-resistant C. jejuni were common(>75%). Multiresistant isolates of C. coli were found in monkeys from all countries and multi-resistant isolates of C. jejuni were found in monkeys from Indonesia. The eradication rate with azithromycin was comparable to that with gentamicin (GEN) by oral administration, and was higher than those with amoxicillin-clavulanic acid (AMC) and chloramphenicol (CHL). Conclusion: From the perspective of zoonosis, we should acknowledge multiresistant Campylobacter spp. isolated from the monkeys as a serious warning.



Antimicrobial resistance (AMR) is one of our most serious health threats. Last year, a report titled Tackling Drug-Resistant Infection Globally: Final Report and Recommendations was published [1]. In this report, O’Neil J. analyses that, by 2050, the death toll could be a staggering one person every three seconds if AMR is not tackled now. This year, WHO published list of bacteria for which new antibiotics are urgently needed [2]. In this list, Campylobacter spp. was categorized as a group of Priority 2: High. Antibiotics are, of course, effective for susceptible bacteria, however, sooner or later, bacteria can develop resistance to them with various mechanisms: the inactivation or modification of the antibiotic; an alteration in the target site of the antibiotic that reduces its binding capacity; the reduced intracellular antibiotic accumulation by decreasing permeability and/or increasing active efflux of the antibiotic; or the modification of metabolic pathways to circumvent the antibiotic effect. Antibiotic resistance can be either plasmid mediated or maintained on the bacterial chromosome. Based on the results from multilocus sequence typing of Campylobacter jejuni, intra- and interspecies recombination plays a large role in generating genetic diversity among Campylobacter jejuni [3]. Natural transformation and conjugation for transmission of antibiotic resistance determinants are well-recognized in Campylobacter spp. [4, 5]. Since Campylobacter spp. acquires resistance determinants by mutation and horizontal gene transfer (transformation, conjugation and transduction), it is not easy to combat this pathogen. Novel approaches such as vaccination for prevention of infection and narrow spectrum (species-, genus- or family-specific) antibiotics for minimization of interspecies horizontal gene transfer are needed to control these types of pathogens. We should consider the strategy of treatment from a higher perspective based on each infection, such as characteristic of bacteria (genetic diversity, intrinsic resistance, and colonization, etc.), the relationship of the host (immunocompromized, outpatient, inpatient, and high-risk group), and site of infection. Furthermore, we should tackle this issue in a One Health approach [6]. One Health recognizes that the health of people is connected to the health of animals and the environment. The goal of One Health is to encourage the collaborative efforts of multiple disciplines-working locally, nationally, and globally-to achieve the best health for people, animals, and our environment.

These results have indicated that antimicrobial resistance threats are just around the corner.



1) O’Neil J.  The review on antimicrobial resistance; London, 2016 https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf

2) WHO: WHO publishes list of bacteria for which new antibiotics are urgently needed http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/

3) Dingle KE, Colles FM, Wareing DR, Ure R, Fox AJ, Bolton FE, Bootsma HJ, Willems RJ, Urwin R, Maiden MC. Multilocus Sequence Typing System for Campylobacter jejuni. J Clin Microbiol. 2001 Jan; 39(1): 14–23. doi:10.1128/JCM.39.1.14-23.2001

4) Vegge CS, Brøndsted L, Ligowska-Marzęta M, Ingmer H. Natural transformation of Campylobacter jejuni occurs beyond limits of growth. PLoS One. 2012;7(9):e45467. doi: 10.1371/journal.pone.0045467. Epub 2012 Sep 26.http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0045467&type=printable

5) Nirdnoy W, Mason CJ, Guerry P. Mosaic structure of a multiple-drug-resistant, conjugative plasmid from Campylobacter jejuni. Antimicrob Agents Chemother. 2005 Jun;49(6):2454-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140535/pdf/1336-04.pdf

6) CDC: One Health. https://www.cdc.gov/onehealth/