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Pharmacology

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

Sander P. van Rijn, Marlanka A. Zuur, Richard Anthony, Bob Wilffert, Richard van Altena, Onno W. Akkerman, Wiel C. M. de Lange, Tjip S. van der Werf, Jos G. W. Kosterink, Jan-Willem C. Alffenaar
Sander P. van Rijn
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Marlanka A. Zuur
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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Richard Anthony
National Institute for Public Health and the Environment, National Mycobacteria Reference Laboratory, Bilthoven, The Netherlands
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Bob Wilffert
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The NetherlandsUniversity of Groningen, Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology & Pharmacoeconomics, Groningen, The Netherlands
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Richard van Altena
University of Groningen, University Medical Center Groningen, Tuberculosis Centre Beatrixoord, Haren, The NetherlandsUniversity of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands
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Onno W. Akkerman
University of Groningen, University Medical Center Groningen, Tuberculosis Centre Beatrixoord, Haren, The NetherlandsUniversity of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands
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Wiel C. M. de Lange
University of Groningen, University Medical Center Groningen, Tuberculosis Centre Beatrixoord, Haren, The NetherlandsUniversity of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands
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Tjip S. van der Werf
University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The NetherlandsUniversity of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, The Netherlands
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Jos G. W. Kosterink
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The NetherlandsUniversity of Groningen, Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, Epidemiology & Pharmacoeconomics, Groningen, The Netherlands
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Jan-Willem C. Alffenaar
University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands
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DOI: 10.1128/AAC.01489-18
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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.

FOOTNOTES

    • Received 17 July 2018.
    • Returned for modification 18 October 2018.
    • Accepted 7 November 2018.
    • Accepted manuscript posted online 19 November 2018.
  • Supplemental material for this article may be found at https://doi.org/10.1128/AAC.01489-18.

  • Copyright © 2019 American Society for Microbiology.

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Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis
Sander P. van Rijn, Marlanka A. Zuur, Richard Anthony, Bob Wilffert, Richard van Altena, Onno W. Akkerman, Wiel C. M. de Lange, Tjip S. van der Werf, Jos G. W. Kosterink, Jan-Willem C. Alffenaar
Antimicrobial Agents and Chemotherapy Jan 2019, 63 (2) e01489-18; DOI: 10.1128/AAC.01489-18

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Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis
Sander P. van Rijn, Marlanka A. Zuur, Richard Anthony, Bob Wilffert, Richard van Altena, Onno W. Akkerman, Wiel C. M. de Lange, Tjip S. van der Werf, Jos G. W. Kosterink, Jan-Willem C. Alffenaar
Antimicrobial Agents and Chemotherapy Jan 2019, 63 (2) e01489-18; DOI: 10.1128/AAC.01489-18
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KEYWORDS

carbapenems
clinical
ertapenem
imipenem
in vitro
in vivo
meropenem
tuberculosis

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