Tags

Type your tag names separated by a space and hit enter

Evaluation of antimicrobial activity of ceftaroline against Clostridium difficile and propensity to induce C. difficile infection in an in vitro human gut model.
J Antimicrob Chemother. 2013 Aug; 68(8):1842-9.JA

Abstract

OBJECTIVES

To examine the effects of exposure to ceftaroline or ceftriaxone on the epidemic Clostridium difficile strain PCR ribotype 027 and the indigenous gut microflora in an in vitro human gut model. Additionally, the MICs of ceftriaxone and ceftaroline for 60 C. difficile isolates were determined.

METHODS

Two triple-stage chemostat gut models were primed with human faeces and exposed to ceftaroline (10 mg/L, twice daily, 7 days) or ceftriaxone (150 mg/L, once daily, 7 days). Populations of indigenous gut microorganisms, C. difficile total viable counts, spore counts, cytotoxin titres and antimicrobial concentrations were monitored throughout. MICs were determined by a standard agar incorporation method.

RESULTS

In the gut model, both ceftaroline and ceftriaxone induced C. difficile spore germination, proliferation and toxin production, although germination occurred 5 days later in the ceftaroline-exposed model. Toxin detection was sustained until the end of the experimental period in both models. No active antimicrobial was detected in vessel 3 of either model, although inhibitory effects on microflora populations were observed. Ceftaroline was ∼8-fold more active against C. difficile than ceftriaxone (geometric mean MICs, 3.38 versus 28.18 mg/L; MIC90s, 4 versus 64 mg/L; and MIC ranges, 0.125-16 versus 8-128 mg/L).

CONCLUSIONS

Ceftaroline, like ceftriaxone, can induce simulated C. difficile infection in a human gut model. However, low in vivo gut concentrations of ceftaroline and increased activity against C. difficile in comparison with ceftriaxone mean that the true propensity of this novel cephalosporin to induce C. difficile infection remains unclear.

Authors+Show Affiliations

Faculty of Health and Human Science, School of Life Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23557928

Citation

Baines, Simon D., et al. "Evaluation of Antimicrobial Activity of Ceftaroline Against Clostridium Difficile and Propensity to Induce C. Difficile Infection in an in Vitro Human Gut Model." The Journal of Antimicrobial Chemotherapy, vol. 68, no. 8, 2013, pp. 1842-9.
Baines SD, Chilton CH, Crowther GS, et al. Evaluation of antimicrobial activity of ceftaroline against Clostridium difficile and propensity to induce C. difficile infection in an in vitro human gut model. J Antimicrob Chemother. 2013;68(8):1842-9.
Baines, S. D., Chilton, C. H., Crowther, G. S., Todhunter, S. L., Freeman, J., & Wilcox, M. H. (2013). Evaluation of antimicrobial activity of ceftaroline against Clostridium difficile and propensity to induce C. difficile infection in an in vitro human gut model. The Journal of Antimicrobial Chemotherapy, 68(8), 1842-9. https://doi.org/10.1093/jac/dkt107
Baines SD, et al. Evaluation of Antimicrobial Activity of Ceftaroline Against Clostridium Difficile and Propensity to Induce C. Difficile Infection in an in Vitro Human Gut Model. J Antimicrob Chemother. 2013;68(8):1842-9. PubMed PMID: 23557928.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evaluation of antimicrobial activity of ceftaroline against Clostridium difficile and propensity to induce C. difficile infection in an in vitro human gut model. AU - Baines,Simon D, AU - Chilton,Caroline H, AU - Crowther,Grace S, AU - Todhunter,Sharie L, AU - Freeman,Jane, AU - Wilcox,Mark H, Y1 - 2013/04/03/ PY - 2013/4/6/entrez PY - 2013/4/6/pubmed PY - 2014/2/8/medline KW - MICs KW - cephalosporins KW - chemostat SP - 1842 EP - 9 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 68 IS - 8 N2 - OBJECTIVES: To examine the effects of exposure to ceftaroline or ceftriaxone on the epidemic Clostridium difficile strain PCR ribotype 027 and the indigenous gut microflora in an in vitro human gut model. Additionally, the MICs of ceftriaxone and ceftaroline for 60 C. difficile isolates were determined. METHODS: Two triple-stage chemostat gut models were primed with human faeces and exposed to ceftaroline (10 mg/L, twice daily, 7 days) or ceftriaxone (150 mg/L, once daily, 7 days). Populations of indigenous gut microorganisms, C. difficile total viable counts, spore counts, cytotoxin titres and antimicrobial concentrations were monitored throughout. MICs were determined by a standard agar incorporation method. RESULTS: In the gut model, both ceftaroline and ceftriaxone induced C. difficile spore germination, proliferation and toxin production, although germination occurred 5 days later in the ceftaroline-exposed model. Toxin detection was sustained until the end of the experimental period in both models. No active antimicrobial was detected in vessel 3 of either model, although inhibitory effects on microflora populations were observed. Ceftaroline was ∼8-fold more active against C. difficile than ceftriaxone (geometric mean MICs, 3.38 versus 28.18 mg/L; MIC90s, 4 versus 64 mg/L; and MIC ranges, 0.125-16 versus 8-128 mg/L). CONCLUSIONS: Ceftaroline, like ceftriaxone, can induce simulated C. difficile infection in a human gut model. However, low in vivo gut concentrations of ceftaroline and increased activity against C. difficile in comparison with ceftriaxone mean that the true propensity of this novel cephalosporin to induce C. difficile infection remains unclear. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/23557928/Evaluation_of_antimicrobial_activity_of_ceftaroline_against_Clostridium_difficile_and_propensity_to_induce_C__difficile_infection_in_an_in_vitro_human_gut_model_ L2 - https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkt107 DB - PRIME DP - Unbound Medicine ER -