Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Eukaryotic Cell
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Antimicrobial Agents and Chemotherapy
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Archive
    • Minireviews
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About AAC
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • AAC Podcast
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Experimental Therapeutics

Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ Mice

Vincent Le Moigne, Clément Raynaud, Flavie Moreau, Christian Dupont, Jérôme Nigou, Olivier Neyrolles, Laurent Kremer, Jean-Louis Herrmann
Vincent Le Moigne
aUVSQ, INSERM, Infection et Inflammation (U1173), Université Paris-Saclay, Montigny-le-Bretonneux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clément Raynaud
bInstitut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Flavie Moreau
cInstitut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Dupont
bInstitut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Université de Montpellier, Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jérôme Nigou
cInstitut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olivier Neyrolles
cInstitut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laurent Kremer
bInstitut de Recherche en Infectiologie de Montpellier, Centre National de la Recherche Scientifique UMR 9004, Université de Montpellier, Montpellier, France
dINSERM, Institut de Recherche en Infectiologie de Montpellier (IRIM), Montpellier, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Laurent Kremer
Jean-Louis Herrmann
aUVSQ, INSERM, Infection et Inflammation (U1173), Université Paris-Saclay, Montigny-le-Bretonneux, France
eHôpital Raymond Poincaré, AP-HP, GHU Paris-Saclay, Garches, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/AAC.00114-20
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

ABSTRACT

Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations of antibiotics, such as bedaquiline and imipenem, although in vitro data have questioned this combination. We report that the efficacy of bedaquiline-imipenem combination treatment relies essentially on the activity of bedaquiline in a C3HeB/FeJ mice model of infection with a rough variant of M. abscessus. The addition of imipenem contributed to clearing the infection in the spleen.

INTRODUCTION

Mycobacterium abscessus is a rapidly growing mycobacterial species whose infections remain very difficult to treat due to the limited panel of available antibiotics (1). Among them, the β-lactams imipenem (IPM) and cefoxitin (FOX) are part of M. abscessus multidrug therapy, along with amikacin (AMK) and clarithromycin (CLR) (2–5). In addition, the development of specific β-lactamase inhibitors, enhancing the efficacy of IPM in vitro and in vivo, broadens the use of IPM in M. abscessus drug therapy (6–8). Other studies highlighted the potential of testing new drug combinations that include IPM and are associated with increased efficacy against M. abscessus infection (6, 9, 10); however, the relevance of the bedaquiline (BDQ) plus IPM combination has been questioned (11). BDQ targets ATP synthase and exhibits activity against a wide panel of M. abscessus clinical isolates in vitro and in infected zebrafish, although its effect is bacteriostatic only (12). A recent study suggested that by reducing the intracellular pool of ATP in M. abscessus isolates, BDQ suppresses the effect of IPM and FOX, although the effect of the BDQ-IPM combination was considered additive (11). This led the investigators to conclude that addition of BDQ to a β-lactam-containing regimen may negatively affect the treatment outcome (11). In comparison, data from the hollow-fiber model highlight that β-lactam is the most active and important part of the M. abscessus treatment regimen (13). Because these studies focused exclusively on the interaction of β-lactams and BDQ in vitro, confirmatory results in a preclinical animal model are warranted.

Herein, we explored the therapeutic efficacy of BDQ and IPM, alone and in combination, using the immunocompetent C3HeB/FeJ mouse model of M. abscessus infection. C3HeB/FeJ mice are highly susceptible to mycobacterial infections, particularly to Mycobacterium tuberculosis due to a deletion of the Ipr1 (intracellular pathogen resistance 1) gene located within the locus sst1 (14, 15). All animal experiments were performed according to ethical guidelines and with ethical committee (no. 047 with agreement A783223) agreement APAFIS 11465.

First, we evaluated the in vitro interaction between BDQ and several β-lactams or CLR against M. abscessus strain CIP104536 in cation-adjusted Mueller-Hinton broth (CaMHB) (Becton, Dickinson, Le Pont-de-Claix, France) using a 2-dimensional microdilution checkerboard method, as previously described (16–19). Our results confirm that the β-lactam plus BDQ combinations are indifferent, as is the case for the CLR-BDQ combination (Table 1).

View this table:
  • View inline
  • View popup
  • Download powerpoint
TABLE 1

Interaction between bedaquiline and other drugs against M. abscessus strain CIP104536T

Next, the performances of pulmonary and intravenous (i.v.) infection routes were compared in C3HeB/FeJ mice. Mice were infected intratracheally using agar bead-embedded bacteria to maintain a persistent infection, as reported previously for Pseudomonas aeruginosa (20). A significant increase in mortality was noted when mice were infected intratracheally with a solution of agar beads containing 2.105 CFU/mouse in 50 μl, leading to only 40% mouse survival at 14 days postinfection (dpi) (see Fig. S1A in the supplemental material), which correlated with an important increase in the CFU at 14 dpi, suggesting accelerated bacterial growth in the lungs (see Fig. S1B). In contrast, persistence occurred for up to 25 days after i.v. infection with 106 CFU/mouse, as evidenced by CFU counting after plating of the organ homogenates (Fig. 1; see also Fig. S2A and B in the supplemental material), although as soon as the injected dose was <106 CFU, persistence in the organs was reduced (Fig. S2B). This represents an important improvement over results found in previously described murine models, characterized by a more rapid bacterial clearance (21–23).

FIG 1
  • Open in new tab
  • Download powerpoint
FIG 1

Bacterial persistence of M. abscessus strain CIP104536T (rough variant) in lungs, spleens, and livers of C3HeB/FeJ mice after i.v. infection in the tail vein with 106 CFU/mouse in a total volume of 200 μl of water containing 0.9% sodium chloride. The following day, 3 mice were euthanized, and whole organs were harvested to determine baseline bacterial burden. Mouse lungs, spleens, and livers were homogenized, serially diluted, and plated onto VCAT (vancomycin, colistin sulfate, amphotericin B, and trimethoprim) chocolate agar plates (bioMérieux, France) and incubated for 5 to 6 days at 37°C before CFU counting. Results are expressed as log10 CFU at 1, 12, and 25 dpi.

The i.v. route of infection was subsequently used to evaluate and compare the activities of BDQ and AMK. Because AMK is bactericidal against M. abscessus isolates and BDQ is bacteriostatic in vitro, we wondered whether BDQ would be more effective than AMK in an in vivo infection model. CFU were significantly reduced in mice receiving BDQ 30 mg/kg (orally) compared with mice receiving AMK 150 mg/kg (subcutaneously) in lungs and spleen at 12 and 25 dpi (Fig. 2A and B). No significant differences were observed between the BDQ- and AMK-treated animals in the spleen at 12 dpi, but bacterial loads in these two groups were significantly lower than those in the control group (oral administration of dimethyl sulfoxide [DMSO]) (Fig. 2C).

FIG 2
  • Open in new tab
  • Download powerpoint
FIG 2

M. abscessus R-infected C3HeB/FeJ mice (9.2 × 105 CFU/mouse) treated with bedaquiline (BDQ) or amikacin (AMK). Bacterial counts in the lungs (A), liver (B), and spleen (C) of C3HeB/FeJ mice infected i.v., as described in Fig. 1. Antibiotic treatment began at 2 dpi. Mice were treated starting on day 2 for 7 days (D12) or 17 days (D25) by daily subcutaneous injections of AMK 150 mg/kg (Mylan Laboratories) in saline solution or daily oral gavage of BDQ 30 mg/kg in a total volume of 200 μl (BDQ solution in DMSO was diluted in 20% 2-hydroxypropyl-β-cyclodextrin). A control group received a daily subcutaneous injection of saline and oral gavage of DMSO containing 20% 2-hydroxypropyl-β-cyclodextrin. All solutions were administered 5 times weekly for later time point. Mice were euthanized 3 days after antibiotic cessation to allow for antibiotic clearance. Furthermore, given the long half-life and high protein binding capacity of BDQ, spleens, livers, and lungs from drug-treated and control mice were homogenized in water supplemented with 10% bovine serum albumin before dilution (30). Experimental groups of mice were evaluated for bacterial burden on day 1 (before treatment started), 12, and 25 as described in Fig. 1. Five mice were used per group. Bacterial load in each group is expressed as log10 CFU ± SD. Differences between means were analyzed by two-way analysis of variance (ANOVA) and the Tukey posttest, allowing for multiple comparisons. n.s., nonsignificant; *, P < 0.05; **, P < 0.01; ***, P < 0.001. Experiment was performed once.

The efficacy of BDQ in this infection model prompted us to compare it with subcutaneous IPM, alone or as a companion drug, for 15 days of treatment. No significant differences were noticed between the animals treated with BDQ alone and the animals treated with BDQ-IPM at 12 and 20 dpi, with the exception of the liver at 12 dpi (Fig. 3A to C), indicating that the overall activity of the BDQ-IPM combination was mainly due to the intrinsic activity of BDQ. In general, BDQ alone or in combination with IPM exhibited increased activity compared with that of IPM alone in the liver and spleen but not in the lungs (Fig. 3). The spleens of treated and untreated mice were weighed as an additional marker of the effectiveness of the various treatments. These measures indicated that only treatments with BDQ plus IPM or IPM alone were associated with lower spleen weights than those of the untreated or BDQ-treated mice (Fig. 3D). Collectively, the reduced bacterial burden and the lower spleen weights represent a marker for improved outcome of the infection.

FIG 3
  • Open in new tab
  • Download powerpoint
FIG 3

M. abscessus R-infected C3HeB/FeJ mice treated (2.7 × 105 CFU/mouse) with bedaquiline (BDQ), imipenem (IPM), or BDQ plus IPM. Bacterial loads in the lungs (A), liver (B), and spleen (C) were determined as reported in Fig. 1. Antibiotic treatment began 2 days after infection. Mice were treated starting on day 2 for 7 days (D12) or 13 days (D20) with twice-daily (i.e., every 12 h) subcutaneous injection of IPM (MSD Laboratories, France) in saline solution at 100 mg/kg or daily oral gavage of BDQ as described in Fig. 2 or IPM-BDQ. Experimental groups of mice were evaluated for bacterial burden on day 1 (before treatment started), 12, and 20 as described in Fig. 1. (D) Relative weights of spleen to mouse. Mouse spleens were weighed at 1, 12, and 20 dpi. Values represent the relative weight of each spleen relative to the weight of the mouse from which it was collected. Five mice were used per experiment. Bacterial load in each group is expressed as log10 CFU ± SD cells. Differences between means were analyzed by two-way ANOVA and the Tukey posttest, allowing for multiple comparisons. n.s., nonsignificant; *, P < 0.05; **, P < 0.01; ***, P < 0.001. Experiment was performed once.

BDQ is a diarylquinoline approved by the Food and Drug Administration and the European Medicines Agency for the treatment of multidrug-resistant tuberculosis. It is bacteriostatic against M. abscessus isolates in vitro, displaying an MIC50 of 0.125 μg/ml and an MIC90 of >16 μg/ml; and epidemiological cutoff values showed that BDQ exhibits moderate activity (16, 24). Discordant results regarding the efficacy of BDQ were generated in various immunocompromised mouse models, raising the question of the influence of immunosuppression on antibiotic efficacy (25, 26). However, efficient responses to BDQ were observed in other animal models, such as zebrafish (12). Two studies reported poor or negative results for BDQ administration against nontuberculous mycobacteria-infected patients (27, 28). However, recent studies showed that the activity of BDQ can be potentiated with adjunctive therapy, thus improving BDQ-based treatments (16, 29). This study provides evidence that treatment with the BDQ-IPM combination remains superior to treatment with IPM alone and equivalent to that with BDQ alone, as judged by the comparable bacterial clearance in the spleens of the mice treated with BDQ-IPM versus BDQ alone.

In summary, the BDQ-IPM combination enhances clearance of the infection. This also supports the importance of evaluating antibiotic activity in combination rather than separately against this highly drug-resistant mycobacterium.

ACKNOWLEDGMENTS

Bedaquiline was a kind gift from C. Happel (NIH AIDS Reagent Program, USA) and from N. Lounis (Janssen Pharmaceuticals, Beerse, Belgium).

We acknowledge N. Véziris and J. van Ingen for helpful comments and critical reading of the manuscript. We thank the members of the Genotoul core facility ANEXPLO (IPBS, Toulouse) for animal experiments.

This study was supported by INSERM, University of Versailles Saint Quentin en Yvelines; the Association Gregory Lemarchal and Vaincre la Mucoviscidose (RIF20180502320) to L.K. and J.L.H.; the Agence Nationale de la Recherche (MyCat ANR-15-CE18-0007-02) to L.K.; CNRS, University of Toulouse, Agence Nationale de la Recherche/Program d’Investissements d’Avenir (ANR-11-EQUIPEX-0003); and the Bettencourt Schueller Foundation.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

J.N., O.N., and J.L.H. designed the project and experiments. V.L.M., C.R., F.M., and C.D. performed the experiments. V.L.M., C.R., J.N., O.N., L.K., and J.L.H. wrote and corrected the manuscript.

FOOTNOTES

    • Received 17 January 2020.
    • Returned for modification 2 March 2020.
    • Accepted 26 March 2020.
    • Accepted manuscript posted online 6 April 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Kwak N,
    2. Dalcolmo MP,
    3. Daley CL,
    4. Eather G,
    5. Gayoso R,
    6. Hasegawa N,
    7. Jhun BW,
    8. Koh WJ,
    9. Namkoong H,
    10. Park J,
    11. Thomson R,
    12. van Ingen J,
    13. Zweijpfenning SMH,
    14. Yim JJ
    . 2019. Mycobacterium abscessus pulmonary disease: individual patient data meta-analysis. Eur Respir J 54:1801991. doi:10.1183/13993003.01991-2018.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Griffith DE,
    2. Aksamit T,
    3. Brown-Elliott BA,
    4. Catanzaro A,
    5. Daley C,
    6. Gordin F,
    7. Holland SM,
    8. Horsburgh R,
    9. Huitt G,
    10. Iademarco MF,
    11. Iseman M,
    12. Olivier K,
    13. Ruoss S,
    14. von Reyn CF,
    15. Wallace RJ, Jr,
    16. Winthrop K, ATS Mycobacterial Diseases Subcommittee, American Thoracic Society, Infectious Disease Society of America
    . 2007. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 175:367–416. doi:10.1164/rccm.200604-571ST.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Haworth CS,
    2. Banks J,
    3. Capstick T,
    4. Fisher AJ,
    5. Gorsuch T,
    6. Laurenson IF,
    7. Leitch A,
    8. Loebinger MR,
    9. Milburn HJ,
    10. Nightingale M,
    11. Ormerod P,
    12. Shingadia D,
    13. Smith D,
    14. Whitehead N,
    15. Wilson R,
    16. Floto RA
    . 2017. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax 72:ii1–ii64. doi:10.1136/thoraxjnl-2017-210927.
    OpenUrlFREE Full Text
  4. 4.↵
    1. Floto RA,
    2. Olivier KN,
    3. Saiman L,
    4. Daley CL,
    5. Herrmann JL,
    6. Nick JA,
    7. Noone PG,
    8. Bilton D,
    9. Corris P,
    10. Gibson RL,
    11. Hempstead SE,
    12. Koetz K,
    13. Sabadosa KA,
    14. Sermet-Gaudelus I,
    15. Smyth AR,
    16. van Ingen J,
    17. Wallace RJ,
    18. Winthrop KL,
    19. Marshall BC,
    20. Haworth CS
    . 2016. US Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary. Thorax 71:88–90. doi:10.1136/thoraxjnl-2015-207983.
    OpenUrlAbstract/FREE Full Text
  5. 5.↵
    1. Lefebvre AL,
    2. Le Moigne V,
    3. Bernut A,
    4. Veckerlé C,
    5. Compain F,
    6. Herrmann JL,
    7. Kremer L,
    8. Arthur M,
    9. Mainardi JL
    . 2017. Inhibition of the β-lactamase BlaMab by avibactam improves the in vitro and in vivo efficacy of imipenem against Mycobacterium abscessus. Antimicrob Agents Chemother 61:e02440-16. doi:10.1128/AAC.02440-16.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Kaushik A,
    2. Ammerman NC,
    3. Lee J,
    4. Martins O,
    5. Kreiswirth BN,
    6. Lamichhane G,
    7. Parrish NM,
    8. Nuermberger EL
    . 2019. In vitro activity of the new β-lactamase inhibitors relebactam and vaborbactam in combination with β-lactams against Mycobacterium abscessus complex clinical isolates. Antimicrob Agents Chemother 63:e02623-18. doi:10.1128/AAC.02623-18.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Dubée V,
    2. Bernut A,
    3. Cortes M,
    4. Lesne T,
    5. Dorchene D,
    6. Lefebvre AL,
    7. Hugonnet JE,
    8. Gutmann L,
    9. Mainardi JL,
    10. Herrmann JL,
    11. Gaillard JL,
    12. Kremer L,
    13. Arthur M
    . 2015. β-Lactamase inhibition by avibactam in Mycobacterium abscessus. J Antimicrob Chemother 70:1051–1058. doi:10.1093/jac/dku510.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Dubée V,
    2. Soroka D,
    3. Cortes M,
    4. Lefebvre AL,
    5. Gutmann L,
    6. Hugonnet JE,
    7. Arthur M,
    8. Mainardi JL
    . 2015. Impact of β-lactamase inhibition on the activity of ceftaroline against Mycobacterium tuberculosis and Mycobacterium abscessus. Antimicrob Agents Chemother 59:2938–2941. doi:10.1128/AAC.05080-14.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Le Run E,
    2. Arthur M,
    3. Mainardi JL
    . 2019. In vitro and intracellular activity of imipenem combined with tedizolid, rifabutin, and avibactam against Mycobacterium abscessus. Antimicrob Agents Chemother 63:e01915-18. doi:10.1128/AAC.01915-18.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Le Run E,
    2. Arthur M,
    3. Mainardi JL
    . 2018. In vitro and intracellular activity of imipenem combined with rifabutin and avibactam against Mycobacterium abscessus. Antimicrob Agents Chemother 62:e00623-18. doi:10.1128/AAC.00623-18.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Lindman M,
    2. Dick T
    . 2019. Bedaquiline eliminates bactericidal activity of β-lactams against Mycobacterium abscessus. Antimicrob Agents Chemother 63:e00827-19. doi:10.1128/AAC.00827-19.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Dupont C,
    2. Viljoen A,
    3. Thomas S,
    4. Roquet-Banères F,
    5. Herrmann JL,
    6. Pethe K,
    7. Kremer L
    . 2017. Bedaquiline inhibits the ATP synthase in Mycobacterium abscessus and is effective in infected zebrafish. Antimicrob Agents Chemother 61:e01225-17. doi:10.1128/AAC.01225-17.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Ferro BE,
    2. Srivastava S,
    3. Deshpande D,
    4. Pasipanodya JG,
    5. van Soolingen D,
    6. Mouton JW,
    7. van Ingen J,
    8. Gumbo T
    . 2016. Failure of the amikacin, cefoxitin, and clarithromycin combination regimen for treating pulmonary Mycobacterium abscessus infection. Antimicrob Agents Chemother 60:6374–6376. doi:10.1128/AAC.00990-16.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Kramnik I,
    2. Dietrich WF,
    3. Demant P,
    4. Bloom BR
    . 2000. Genetic control of resistance to experimental infection with virulent Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 97:8560–8565. doi:10.1073/pnas.150227197.
    OpenUrlAbstract/FREE Full Text
  15. 15.↵
    1. Pan H,
    2. Yan BS,
    3. Rojas M,
    4. Shebzukhov YV,
    5. Zhou H,
    6. Kobzik L,
    7. Higgins DE,
    8. Daly MJ,
    9. Bloom BR,
    10. Kramnik I
    . 2005. Ipr1 gene mediates innate immunity to tuberculosis. Nature 434:767–772. doi:10.1038/nature03419.
    OpenUrlCrossRefPubMedWeb of Science
  16. 16.↵
    1. Ruth MM,
    2. Sangen JJN,
    3. Remmers K,
    4. Pennings LJ,
    5. Svensson E,
    6. Aarnoutse RE,
    7. Zweijpfenning SMH,
    8. Hoefsloot W,
    9. Kuipers S,
    10. Magis-Escurra C,
    11. Wertheim HFL,
    12. van Ingen J
    . 2019. A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria. J Antimicrob Chemother 74:935–943. doi:10.1093/jac/dky526.
    OpenUrlCrossRef
  17. 17.↵
    1. Odds FC
    . 2003. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52:1. doi:10.1093/jac/dkg301.
    OpenUrlCrossRefPubMedWeb of Science
  18. 18.↵
    1. Li W,
    2. Sanchez-Hidalgo A,
    3. Jones V,
    4. de Moura VC,
    5. North EJ,
    6. Jackson M
    . 2017. Synergistic interactions of MmpL3 inhibitors with antitubercular compounds in vitro. Antimicrob Agents Chemother 61:e02399-16. doi:10.1128/AAC.02399-16.
    OpenUrlAbstract/FREE Full Text
  19. 19.↵
    Clinical and Laboratory Standards Institute. 2018. Susceptibility testing of mycobacteria, Nocardiae spp., and other aerobic actinomycetes—3rd ed. CLSI standard M24. Clinical and Laboratory Standards Institute, Wayne, PA.
  20. 20.↵
    1. Cigana C,
    2. Lorè NI,
    3. Riva C,
    4. De Fino I,
    5. Spagnuolo L,
    6. Sipione B,
    7. Rossi G,
    8. Nonis A,
    9. Cabrini G,
    10. Bragonzi A
    . 2016. Tracking the immunopathological response to Pseudomonas aeruginosa during respiratory infections. Sci Rep 6:21465. doi:10.1038/srep21465.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Bernut A,
    2. Le Moigne V,
    3. Lesne T,
    4. Lutfalla G,
    5. Herrmann JL,
    6. Kremer L
    . 2014. In vivo assessment of drug efficacy against Mycobacterium abscessus using the embryonic zebrafish test system. Antimicrob Agents Chemother 58:4054–4063. doi:10.1128/AAC.00142-14.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Le Moigne V,
    2. Rottman M,
    3. Goulard C,
    4. Barteau B,
    5. Poncin I,
    6. Soismier N,
    7. Canaan S,
    8. Pitard B,
    9. Gaillard JL,
    10. Herrmann JL
    . 2015. Bacterial phospholipases C as vaccine candidate antigens against cystic fibrosis respiratory pathogens: the Mycobacterium abscessus model. Vaccine 33:2118–2124. doi:10.1016/j.vaccine.2015.03.030.
    OpenUrlCrossRefPubMed
  23. 23.↵
    1. Ordway D,
    2. Henao-Tamayo M,
    3. Smith E,
    4. Shanley C,
    5. Harton M,
    6. Troudt J,
    7. Bai X,
    8. Basaraba RJ,
    9. Orme IM,
    10. Chan ED
    . 2008. Animal model of Mycobacterium abscessus lung infection. J Leukoc Biol 83:1502–1511. doi:10.1189/jlb.1007696.
    OpenUrlCrossRefPubMedWeb of Science
  24. 24.↵
    1. Pang Y,
    2. Zheng H,
    3. Tan Y,
    4. Song Y,
    5. Zhao Y
    . 2017. In vitro activity of bedaquiline against nontuberculous mycobacteria in China. Antimicrob Agents Chemother 61:e02627-16. doi:10.1128/AAC.02627-16.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Lerat I,
    2. Cambau E,
    3. Roth Dit Bettoni R,
    4. Gaillard JL,
    5. Jarlier V,
    6. Truffot C,
    7. Veziris N
    . 2014. In vivo evaluation of antibiotic activity against Mycobacterium abscessus. J Infect Dis 209:905–912. doi:10.1093/infdis/jit614.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Obregón-Henao A,
    2. Arnett KA,
    3. Henao-Tamayo M,
    4. Massoudi L,
    5. Creissen E,
    6. Andries K,
    7. Lenaerts AJ,
    8. Ordway DJ
    . 2015. Susceptibility of Mycobacterium abscessus to antimycobacterial drugs in preclinical models. Antimicrob Agents Chemother 59:6904–6912. doi:10.1128/AAC.00459-15.
    OpenUrlAbstract/FREE Full Text
  27. 27.↵
    1. Philley JV,
    2. Wallace RJ, Jr.,
    3. Benwill JL,
    4. Taskar V,
    5. Brown-Elliott BA,
    6. Thakkar F,
    7. Aksamit TR,
    8. Griffith DE
    . 2015. Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest 148:499–506. doi:10.1378/chest.14-2764.
    OpenUrlCrossRef
  28. 28.↵
    1. Zweijpfenning SMH,
    2. Schildkraut JA,
    3. Coolen JPM,
    4. Ruesen C,
    5. Koenraad E,
    6. Janssen A,
    7. Ruth MM,
    8. de Jong AS,
    9. Kuipers S,
    10. Aarnoutse RE,
    11. Magis-Escurra C,
    12. Hoefsloot W,
    13. van Ingen J
    . 2019. Failure with acquired resistance of an optimised bedaquiline-based treatment regimen for pulmonary Mycobacterium avium complex disease. Eur Respir J 54:1900118. doi:10.1183/13993003.00118-2019.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Viljoen A,
    2. Raynaud C,
    3. Johansen MD,
    4. Roquet-Banères F,
    5. Herrmann JL,
    6. Daher W,
    7. Kremer L
    . 2019. Verapamil improves the activity of bedaquiline against Mycobacterium abscessus in vitro and in macrophages. Antimicrob Agents Chemother 63:e00705-19. doi:10.1128/AAC.00705-19.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Lenaerts AJ,
    2. Hoff D,
    3. Aly S,
    4. Ehlers S,
    5. Andries K,
    6. Cantarero L,
    7. Orme IM,
    8. Basaraba RJ
    . 2007. Location of persisting mycobacteria in a Guinea pig model of tuberculosis revealed by r207910. Antimicrob Agents Chemother 51:3338–3345. doi:10.1128/AAC.00276-07.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
Download PDF
Citation Tools
Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ Mice
Vincent Le Moigne, Clément Raynaud, Flavie Moreau, Christian Dupont, Jérôme Nigou, Olivier Neyrolles, Laurent Kremer, Jean-Louis Herrmann
Antimicrobial Agents and Chemotherapy May 2020, 64 (6) e00114-20; DOI: 10.1128/AAC.00114-20

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ Mice
(Your Name) has forwarded a page to you from Antimicrobial Agents and Chemotherapy
(Your Name) thought you would be interested in this article in Antimicrobial Agents and Chemotherapy.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ Mice
Vincent Le Moigne, Clément Raynaud, Flavie Moreau, Christian Dupont, Jérôme Nigou, Olivier Neyrolles, Laurent Kremer, Jean-Louis Herrmann
Antimicrobial Agents and Chemotherapy May 2020, 64 (6) e00114-20; DOI: 10.1128/AAC.00114-20
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • INTRODUCTION
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

C3HeB/FeJ mice
Mycobacterium abscessus
bedaquiline
cystic fibrosis
imipenem

Related Articles

Cited By...

About

  • About AAC
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • AAC Podcast
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #AACJournal

@ASMicrobiology

       

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0066-4804; Online ISSN: 1098-6596