2447. Ertapenem and faropenem for the treatment of drug resistant tuberculosis
Session: Poster Abstract Session: Treatment of AMR Infections
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • Poster2447.pdf (290.2 kB)
  • Background: Carbapenems are a class of beta-lactam antibiotics which include imipenem, meropenem and ertapenem. More recently, a new oral carbapenem (faropenem) have been marketed in a limited number of countries (in particular, India and Japan). Emerging evidence demonstrates that they target the mycobacterial cell wall, providing an alternative treatment for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), where options are limited. Compared to imipenem and meropenem (both only available as intravenous formulations), ertapenem (once daily administration) and faropenem (oral) are much more attractive alternatives for ambulatory or homecare treatment. However, there is a paucity of data on their efficacy against M. tuberculosis. The aim of this project was to test the in vitro activity of ertapenem and faropenem (with and without the addition of amoxicillin/clavulanate) against different clinical isolates of M. tuberculosis and the reference strain H37RV, to better understand their potential role as additional antibiotics in the management of drug resistant TB.

    Methods: Twenty isolates in total (19 clinical isolates, including MDR and XDR strains, plus H37Rv) were tested against different concentrations of ertapenem and faropenem (with and without the addition of amoxicillin/clavulanate). Susceptibility testing was performed using two different methods (BACTEC960 and broth microdilution). A degradation assay was also performed to evaluate the stability of ertapenem.

    Results: Eighteen out of twenty samples were resistant to the highest concentration of ertapenem tested (including the addition of amoxicillin/clavulanate). Half of the samples tested showed some degree of susceptibility to faropenem and the addition of amoxicillin/clavulanate further reduced the MIC level in seven isolates.

    Conclusion: The results from this project have highlighted a significant level of in vitro resistance to ertapenem, whilst the clinical isolates have shown different degrees of susceptibility to faropenem. Although promising agents (in particular, faropenem), carbapenems will remain a third line choice to be used only in cases of XDR TB. There is currently no evidence to prefer the use of ertapenem despite its once daily administration.

    Giovanni Satta, MBBS MSc MBA FRCPath1,2, Ximena Gonzalo, MBBS FRCPath3, Julio Ortiz Canseco, PhD4, Emmanuel Wey, MBBS MSc MRCPCH FRCPath4,5, Francis Drobniewski, Professor3 and Timothy D McHugh, Professor4, (1)Charing Cross Hospital, Microbiology, Imperial College Healthcare NHS Trust, London, United Kingdom, (2)Centre for Clinical Microbiology, University College London, London, United Kingdom, (3)Imperial College London, London, United Kingdom, (4)University College London, London, United Kingdom, (5)Royal Free London NHS Foundation Trust, London, United Kingdom

    Disclosures:

    G. Satta, None

    X. Gonzalo, None

    J. Ortiz Canseco, None

    E. Wey, None

    F. Drobniewski, None

    T. D. McHugh, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.