Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan 29;63(2):e01489-18.
doi: 10.1128/AAC.01489-18. Print 2019 Feb.

Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis

Sander P van Rijn #  1 , Marlanka A Zuur #  1 , Richard Anthony  2 , Bob Wilffert  1   3 , Richard van Altena  4   5 , Onno W Akkerman  4   5 , Wiel C M de Lange  4   5 , Tjip S van der Werf  5   6 , Jos G W Kosterink  1   3 , Jan-Willem C Alffenaar  7
Affiliations

Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis

Sander P van Rijn et al. Antimicrob Agents Chemother. .

Abstract

Multi- and extensively drug-resistant tuberculosis (M/XDR-TB) has become an increasing threat not only in countries where the TB burden is high but also in affluent regions, due to increased international travel and globalization. Carbapenems are earmarked as potentially active drugs for the treatment of Mycobacterium tuberculosis To better understand the potential of carbapenems for the treatment of M/XDR-TB, the aim of this review was to evaluate the literature on currently available in vitro, in vivo, and clinical data on carbapenems in the treatment of M. tuberculosis and to detect knowledge gaps, in order to target future research. In February 2018, a systematic literature search of PubMed and Web of Science was performed. Overall, the results of the studies identified in this review, which used a variety of carbapenem susceptibility tests on clinical and laboratory strains of M. tuberculosis, are consistent. In vitro, the activity of carbapenems against M. tuberculosis is increased when used in combination with clavulanate, a BLaC inhibitor. However, clavulanate is not commercially available alone, and therefore, it is impossible in practice to prescribe carbapenems in combination with clavulanate at this time. Few in vivo studies have been performed, including one prospective, two observational, and seven retrospective clinical studies to assess the effectiveness, safety, and tolerability of three different carbapenems (imipenem, meropenem, and ertapenem). We found no clear evidence at the present time to select one particular carbapenem among the different candidate compounds to design an effective M/XDR-TB regimen. Therefore, more clinical evidence and dose optimization substantiated by hollow-fiber infection studies are needed to support repurposing carbapenems for the treatment of M/XDR-TB.

Keywords: carbapenems; clinical; ertapenem; imipenem; in vitro; in vivo; meropenem; tuberculosis.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Literature selection process flow chart
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. World Health Organization. 2017. Global tuberculosis report 2017. http://www.who.int/tb/publications/global_report/gtbr2017_main_text.pdf.
    1. Falzon D, Schünemann HJ, Harausz E, González-Angulo L, Lienhardt C, Jaramillo E, Weyer K. 2017. World Health Organization treatment guidelines for drug-resistant tuberculosis, 2016 update. Eur Respir J 49:1602308. doi:10.1183/13993003.02308-2016. - DOI - PMC - PubMed
    1. Nguyen TVA, Anthony RM, Bañuls AL, Vu DH, Alffenaar JC. 2017. Bedaquiline resistance: its emergence, mechanism and prevention. Clin Infect Dis 66:1625–1630. doi:10.1093/cid/cix992. - DOI - PubMed
    1. Alsaad N, Wilffert B, van Altena R, de Lange WC, van der Werf TS, Kosterink JG, Alffenaar JW. 2013. Potential antimicrobial agents for the treatment of multidrug-resistant tuberculosis. Eur Respir J 43:884–897. doi:10.1183/09031936.00113713. - DOI - PubMed
    1. van der Paardt AF, Wilffert B, Akkerman OW, de Lange WC, van Soolingen D, Sinha B, van der Werf TS, Kosterink JG, Alffenaar JW. 2015. Evaluation of macrolides for possible use against multidrug-resistant Mycobacterium tuberculosis. Eur Respir J 46:444–455. doi:10.1183/09031936.00147014. - DOI - PubMed

MeSH terms

LinkOut - more resources