Skip to main content

Advertisement

SpringerLink
Log in

Ceftriaxone promotes the emergence of AmpC-overproducing Enterobacteriaceae in gut microbiota from hospitalized patients

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Epidemiological data suggest that ceftriaxone may promote the emergence of commensal AmpC-overproducing Enterobacteriaceae because of a high biliary excretion. We tested this hypothesis in hospitalized patients either treated by ceftriaxone alone or receiving no antibiotics. Hospitalized patients with no previous antibiotics or hospitalization in the last 3 months, treated only with ceftriaxone, were prospectively included. For each ceftriaxone-treated patient, a control patient receiving no antibiotics was included. Clinical data and stools were collected at T0 (before antibiotics) and T1 (at the end of ceftriaxone treatment or at discharge) and T2 (3–6 months after T1) for the ceftriaxone-treated patients and at T0 and T1 for control patients. Third-generation cephalosporin-resistant Enterobacteriaceae were detected, identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), and characterized genetically. Clonal relatedness was evaluated by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). Fifteen ceftriaxone and 22 control patients were included. Patients’ characteristics did not differ. At T0, 2/15 ceftriaxone-treated versus 1/22 control patients carried third-generation cephalosporin-resistant Enterobacteriaceae (p = 0.6). At T1, 4/15 (27%) ceftriaxone-treated patients carried AmpC producers versus 0/22 control patients (p = 0.02). Additionally, two and three subjects carried extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in the ceftriaxone and control groups, respectively (p = 1). At T2, three ceftriaxone-treated patients still carried AmpC-producing Enterobacteriaceae with the same RAPD profile as at T1. In hospitalized subjects with no other selective pressure, treatment by ceftriaxone alone promotes the gut colonization by AmpC-overproducing Enterobacteriaceae in over a quarter of patients, with a persistent carriage after the end of antibiotic exposure. The ecological impact of ceftriaxone should not be underestimated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jacoby GA (2009) AmpC beta-lactamases. Clin Microbiol Rev 22:161–182. https://doi.org/10.1128/CMR.00036-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pitout JDD, Laupland KB (2008) Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 8:159–166. https://doi.org/10.1016/S1473-3099(08)70041-0

    Article  CAS  PubMed  Google Scholar 

  3. Nordmann P, Naas T, Poirel L (2011) Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 17:1791–1798. https://doi.org/10.3201/eid1710.110655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Grohs P, Kernéis S, Sabatier B, Lavollay M, Carbonnelle E, Rostane H et al (2014) Fighting the spread of AmpC-hyperproducing Enterobacteriaceae: beneficial effect of replacing ceftriaxone with cefotaxime. J Antimicrob Chemother 69:786–789. https://doi.org/10.1093/jac/dkt403

    Article  CAS  PubMed  Google Scholar 

  5. Muller A, Lopez-Lozano JM, Bertrand X, Talon D (2004) Relationship between ceftriaxone use and resistance to third-generation cephalosporins among clinical strains of Enterobacter cloacae. J Antimicrob Chemother 54:173–177. https://doi.org/10.1093/jac/dkh282

    Article  CAS  PubMed  Google Scholar 

  6. Fantin B, Duval X, Massias L, Alavoine L, Chau F, Retout S et al (2009) Ciprofloxacin dosage and emergence of resistance in human commensal bacteria. J Infect Dis 200:390–398. https://doi.org/10.1086/600122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. de Lastours V, Cambau E, Guillard T, Marcade G, Chau F, Fantin B (2012) Diversity of individual dynamic patterns of emergence of resistance to quinolones in Escherichia coli from the fecal flora of healthy volunteers exposed to ciprofloxacin. J Infect Dis 206:1399–1406. https://doi.org/10.1093/infdis/jis511

    Article  PubMed  Google Scholar 

  8. Drieux L, Brossier F, Sougakoff W, Jarlier V (2008) Phenotypic detection of extended-spectrum β-lactamase production in Enterobacteriaceae: review and bench guide. Clin Microbiol Infect 14:90–103. https://doi.org/10.1111/j.1469-0691.2007.01846.x

    Article  CAS  PubMed  Google Scholar 

  9. Dallenne C, Da Costa A, Decré D, Favier C, Arlet G (2010) Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae. J Antimicrob Chemother 65:490–495. https://doi.org/10.1093/jac/dkp498

    Article  CAS  PubMed  Google Scholar 

  10. Pérez-Pérez FJ, Hanson ND (2002) Detection of plasmid-mediated AmpC beta-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol 40:2153–2162

    Article  PubMed  PubMed Central  Google Scholar 

  11. Martin B, Garriga M, Hugas M, Aymerich T (2005) Genetic diversity and safety aspects of enterococci from slightly fermented sausages. J Appl Microbiol 98:1177–1190. https://doi.org/10.1111/j.1365-2672.2005.02555.x

    Article  CAS  PubMed  Google Scholar 

  12. de Lastours V, Chau F, Roy C, Larroque B, Fantin B (2014) Emergence of quinolone resistance in the microbiota of hospitalized patients treated or not with a fluoroquinolone. J Antimicrob Chemother 69:3393–3400. https://doi.org/10.1093/jac/dku283

    Article  PubMed  Google Scholar 

  13. Tacconelli E, Cataldo MA, Dancer SJ, De Angelis G, Falcone M, Frank U et al (2014) ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients. Clin Microbiol Infect 20(Suppl 1):1–55. https://doi.org/10.1111/1469-0691.12427

    Article  PubMed  Google Scholar 

  14. de Lastours V, Bleibtreu A, Chau F, Burdet C, Duval X, Denamur E et al (2014) Quinolone-resistant Escherichia coli from the faecal microbiota of healthy volunteers after ciprofloxacin exposure are highly adapted to a commensal lifestyle. J Antimicrob Chemother 69:761–768. https://doi.org/10.1093/jac/dkt422

    Article  PubMed  Google Scholar 

  15. Ruppé E, Armand-Lefèvre L, Estellat C, Consigny PH, El Mniai A, Boussadia Y et al (2015) High rate of acquisition but short duration of carriage of multidrug-resistant Enterobacteriaceae after travel to the tropics. Clin Infect Dis 61:593–600. https://doi.org/10.1093/cid/civ333

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was presented as a poster at the 27th European Congress on Clinical Microbiology and Infectious Diseases (ECCMID) meeting (Vienna, Austria, 22–25 April 2017).

Funding

The research leading to these results has received funding from the European Union (EU) FP7 health program Evolution and Transfer of Antibiotic Resistance (EvoTAR #282004).

Author information

Author notes

  1. Vincent Cattoir

    Present address: Service de Bactériologie-Hygiène Hospitalière, CHU de Rennes, Rennes, France

Authors and Affiliations

  1. IAME, UMR-1137, INSERM and Université Paris Diderot, Sorbonne Paris Cité , Paris, France

    Victoire de Lastours, Hervé Jacquier, Cindy Eyma, Françoise Chau & Bruno Fantin

  2. Service de Médecine Interne, Hôpital Beaujon, APHP, 100 Boulevard Général Leclerc, 92100, Clichy, France

    Victoire de Lastours, Tiphaine Goulenok & Bruno Fantin

  3. Service de Microbiologie, CHU de Caen, Caen, France

    François Guérin & Vincent Cattoir

  4. Université de Caen Normandie, EA4655, Caen, France

    François Guérin & Vincent Cattoir

  5. Service de Microbiologie, Hôpital Lariboisière, APHP, Paris, France

    Hervé Jacquier

Authors
  1. Victoire de Lastours
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiphaine Goulenok
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. François Guérin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hervé Jacquier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cindy Eyma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Françoise Chau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vincent Cattoir
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bruno Fantin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Victoire de Lastours.

Ethics declarations

Conflict of interest

All authors declare they have no conflict of interest concerning this work.

Ethical approval

This work was approved by the French National Institutional Review Board (IRB 00008522; clinical trial: NCT02031588).

Informed consent

All patients gave informed consent, according to French Law and the approval from the French National Institutional Review Board (IRB 00008522).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Lastours, V., Goulenok, T., Guérin, F. et al. Ceftriaxone promotes the emergence of AmpC-overproducing Enterobacteriaceae in gut microbiota from hospitalized patients. Eur J Clin Microbiol Infect Dis 37, 417–421 (2018). https://doi.org/10.1007/s10096-018-3186-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-018-3186-x

Keywords

Search

Navigation