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Letter to the Editor

Reply to Nevez and Le Gal, “Caspofungin and Pneumocystis Pneumonia: It Is Time To Go Ahead”

Amanda Luraschi, Sophie Richard, Philippe Marcel Hauser
Amanda Luraschi
aInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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Sophie Richard
aInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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Philippe Marcel Hauser
aInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
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  • ORCID record for Philippe Marcel Hauser
DOI: 10.1128/AAC.01320-19
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REPLY

We thank Nevez and Le Gal for their interest in our work and for underscoring its importance (1). Our results strongly suggest that Pneumocystis jirovecii, which infects humans, is sensitive to caspofungin, as are the Pneumocystis species that infect rodents used as models. Thus, we fully agree with Nevez and Le Gal that the usefulness of caspofungin to treat Pneumocystis pneumonia should be considered for clinical use. In addition, the sensitivity of P. jirovecii to the other echinocandins used clinically will have to be characterized. Indeed, Saccharomyces cerevisiae harbors three differentially regulated genes encoding the target of the echinocandins, the catalytic subunit of the 1,3-β-glucan synthase. Despite close homology, these enzymes present drastically distinct sensitivities to the different echinocandins, namely, caspofungin, anidulafungin, and micafungin (1–3). The Pneumocystis species infecting rodents proved to be sensitive to the three echinocandins (4, 5). Nevertheless, because the homology between the enzymes of the different Pneumocystis species is similar to that between the three S. cerevisiae enzymes (1), one cannot exclude the possibility that P. jirovecii is insensitive to anidulafungin and micafungin.

FOOTNOTES

  • This is a response to a letter by Nevez and Le Gal (https://doi.org/10.1128/AAC.01296-19).

  • Copyright © 2019 American Society for Microbiology.

All Rights Reserved.

REFERENCES

  1. 1.↵
    1. Luraschi A,
    2. Richard S,
    3. Hauser PM
    . 2018. Site-directed mutagenesis of the 1,3-β glucan synthase catalytic subunit of Pneumocystis jirovecii and susceptibility assays suggests its sensitivity to caspofungin. Antimicrob Agents Chemother 62:e01159-18. doi:10.1128/AAC.01159-18.
    OpenUrlAbstract/FREE Full Text
  2. 2.↵
    1. Markovich S,
    2. Yekutiel A,
    3. Shalit I,
    4. Shadkchan Y,
    5. Osherov N
    . 2004. Genomic approach to identification of mutations affecting caspofungin susceptibility in Saccharomyces cerevisiae. Antimicrob Agents Chemother 48:3871–3876. doi:10.1128/AAC.48.10.3871-3876.2004.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    1. Johnson ME,
    2. Katiyar SK,
    3. Edlind TD
    . 2011. New Fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species. Antimicrob Agents Chemother 55:3774–3781. doi:10.1128/AAC.01811-10.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Cushion MT,
    2. Linke MJ,
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    4. Sesterhenn T,
    5. Collins MS,
    6. Lynch K,
    7. Brubaker R,
    8. Walzer PD
    . 2010. Echinocandin treatment of Pneumocystis pneumonia in rodent models depletes cysts leaving trophic burdens that cannot transmit the infection. PLoS One 5:e8524. doi:10.1371/journal.pone.0008524.
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    1. Lobo ML,
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    3. de Sousa B,
    4. Cardoso F,
    5. Cushion MT,
    6. Antunes F,
    7. Matos O
    . 2013. Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for Pneumocystis pneumonia: a pilot study in mice. PLoS One 8:e70619. doi:10.1371/journal.pone.0070619.
    OpenUrlCrossRef
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Reply to Nevez and Le Gal, “Caspofungin and Pneumocystis Pneumonia: It Is Time To Go Ahead”
Amanda Luraschi, Sophie Richard, Philippe Marcel Hauser
Antimicrobial Agents and Chemotherapy Sep 2019, 63 (10) e01320-19; DOI: 10.1128/AAC.01320-19

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Reply to Nevez and Le Gal, “Caspofungin and Pneumocystis Pneumonia: It Is Time To Go Ahead”
Amanda Luraschi, Sophie Richard, Philippe Marcel Hauser
Antimicrobial Agents and Chemotherapy Sep 2019, 63 (10) e01320-19; DOI: 10.1128/AAC.01320-19
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