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Experimental Therapeutics

Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia

Lynn Miesel, Melanie T. Cushion, Alan Ashbaugh, Santiago R. Lopez, Voon Ong
Lynn Miesel
aPharmacology Discovery Services, Taipei, Taiwan
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Melanie T. Cushion
bUniversity of Cincinnati College of Medicine, Cincinnati, Ohio, USA
cCincinnati VAMC, Cincinnati, Ohio, USA
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Alan Ashbaugh
bUniversity of Cincinnati College of Medicine, Cincinnati, Ohio, USA
cCincinnati VAMC, Cincinnati, Ohio, USA
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Santiago R. Lopez
dTransPharm Preclinical Solutions, Inc., Jackson, Michigan, USA
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Voon Ong
eCidara Therapeutics, Inc., San Diego, California, USA
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DOI: 10.1128/AAC.01992-20
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ABSTRACT

Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive therapies. Current approaches to antifungal prophylaxis require multiple agents to cover these key fungi. Rezafungin, a novel echinocandin designed for next-generation properties (e.g., greater stability and long-acting pharmacokinetics for once-weekly dosing), has demonstrated in vitro activity against Candida and Aspergillus spp. and efficacy against Pneumocystis spp. biofilms. Rezafungin was evaluated in in vivo studies of prophylactic efficacy using immunosuppressed mouse models of invasive candidiasis, aspergillosis, and Pneumocystis pneumonia. Rezafungin reduction of Candida CFU burden was generally greater with increasing drug concentrations (5, 10, or 20 mg/kg) and when rezafungin was administered closer to the time of fungal challenge (day −1, −3, or −5). Similarly, in the aspergillosis model, survival rates increased with drug concentrations and when rezafungin was administered closer to the time of fungal challenge. Against Pneumocystis murina, rezafungin significantly reduced trophic nuclei and asci counts at all doses tested. Rezafungin prevented infection at the two higher doses compared to vehicle and had comparable activity to the active control trimethoprim-sulfamethoxazole at human equivalent doses for prevention. These findings support phase 3 development of rezafungin and the potential for single-agent prophylaxis against invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii.

INTRODUCTION

Antifungal prophylaxis is an important strategy against invasive fungal disease (IFD) in patients at risk for opportunistic infections, such as recipients of allogeneic blood or marrow transplantation or solid organ transplantation, as well as patients with hematological disorders undergoing chemotherapy (1–6). For such patient populations, antifungal prophylaxis is recommended to prevent infections caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii (7–9). An ideal antifungal prophylaxis regimen would provide fitting coverage of the most prevalent opportunistic pathogens without obstructing or complicating therapy due to toxicity, intolerability, or drug-drug interactions (DDIs).

While recommendations and clinical trial data are available to guide antifungal prophylaxis (7, 10–14), there is no single approach as prophylaxis must be customized to the needs of a given patient, as well as local fungal epidemiology and susceptibility. Current strategies to protect against these most commonly encountered pathogens generally enlist an azole (one with mold activity if there is risk of Aspergillus) and trimethoprim-sulfamethoxazole (SXT) for Pneumocystis jirovecii pneumonia (PCP) (7, 9, 10). Considerations when personalizing azole therapy include pharmacokinetic variability, oral tolerability, and safety (such as liver toxicity and effects on the QT interval), as well as DDIs (15, 16). For SXT, personalizing therapy may include modifications to antifungal prophylaxis and/or primary treatment to mitigate SXT-associated fever, rash resembling GVHD, nephrotoxicity, or myelosuppression (8). Unmet needs in the current approach to antifungal prophylaxis may lead to gaps in protection against IFD or complications in treatment of primary disease, such as when dosing is disrupted or when adverse effects (AEs) and DDIs occur.

With the advent of newer therapies for treatment of primary disease, many of which introduce new or increased risks of IFD and DDIs with antifungal agents, patient-level considerations have expanded in scope and complexity. Recent examples include the increased incidence of PCP observed with Bruton’s tyrosine kinase inhibitors (ibrutinib and acalabrutinib) and IFD associated with immune checkpoint inhibitors (17–21). Arguably, the greatest impact of newer treatments on antifungal prophylaxis may be from DDIs caused by CYP interactions or other mechanisms that may contraindicate concomitant use (16, 22). The AEs of newer treatments or their management with corticosteroids or other immunosuppressants may also increase infection risk (23–26). Additional experience with newer treatments will help to guide antifungal prophylaxis management. At the same time, newer antifungal options and strategies are needed to support the continuous advancements in treatment of hematologic diseases and in immunosuppressive therapies.

Rezafungin is a novel echinocandin in development for the treatment and prevention of invasive candidiasis, with a phase 3 treatment trial (ReSTORE NCT03667690) and a phase 3 prophylaxis trial (ReSPECT NCT04368559) under way. While the current approach to antifungal prophylaxis requires multiple agents to cover the key target pathogens, rezafungin has demonstrated in vitro activity against Candida and Aspergillus species, including azole-resistant strains of Aspergillus fumigatus, as well as efficacy against Pneumocystis biofilms (27–34). Rezafungin is distinguished by a long half-life and front-loaded, high plasma drug exposures that allow for the once-weekly intravenous dosing regimen in clinical development. Rezafungin administered once weekly has demonstrated safety and tolerability consistent with that of its echinocandin class. Preclinical evaluation demonstrated rezafungin chemical and metabolic stability and lack of hepatotoxicity, in contrast to anidulafungin (35, 36). Phase 1 trials of rezafungin showed a lack of effect on the QT interval and low risk of DDIs with commonly used drugs (37, 38). To further contribute to these data, this series of in vivo studies evaluated the efficacy of rezafungin in prophylactic mouse models of invasive fungal infections caused by Candida, Aspergillus, and Pneumocystis in immunosuppressed mice.

(Data from these studies were preliminarily presented at the 2017 European Hematology Association meeting [Madrid, Spain].)

RESULTS

Prevention of Candida infection.Rezafungin prophylaxis in an immunosuppressed mouse model of invasive candidiasis demonstrated decreases in the Candida CFU burden, an effect that increased with rezafungin concentrations and when prophylaxis administration occurred closer to challenge (day −1 > day −3 > day −5; Fig. 1). C. albicans was completely cleared in all animals given rezafungin 20 mg/kg, except for one animal that had prophylaxis administered on day −3. At the lower doses (10 and 5 mg/kg), bioburden reduction when prophylaxis was administered on day −5 (similar to day −15 for humans as described in Materials and Methods) was not significantly different than vehicle. However, when prophylaxis administration occurred closer to challenge, on day −3 or day −1, the 10-mg/kg rezafungin groups had no measurable CFU, and the 5-mg/kg groups showed significantly lower fungal burden than did the vehicle control, indicating a dose response as well as correlation with timing of prophylaxis administration (day −1 > day −3 > day −5).

FIG 1
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FIG 1

Clearance and significant decreases in kidney CFU burden of Candida (C. albicans, MIC = 0.03 µg/ml) in mice after administration of rezafungin prophylaxis.

Prevention of Aspergillus infection.Rezafungin prophylaxis against A. fumigatus in the immunosuppressed mouse model of invasive aspergillosis demonstrated protection at doses of 10 and 20 mg/kg, with all animals in these groups surviving the 14-day postchallenge period regardless of when prophylaxis was administered (Fig. 2, right). In the group given the lowest dose tested (rezafungin 5 mg/kg), survival increased when prophylaxis administration occurred closer to challenge (day −1 > day −3 > day −5; Fig. 2, left).

FIG 2
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FIG 2

Survival rates in mice challenged with Aspergillus (A. fumigatus, MEC = 0.0078 µg/ml) after administration of rezafungin prophylaxis. (Left) 5 mg/kg; (right) 10 or 20 mg/kg. P < 0.05 for all dosing arms, except for 5 mg/kg, day –5 (P = 0.182).

Prevention of PCP.Rezafungin prophylaxis in the immunosuppressed mouse model of PCP demonstrated significantly reduced trophic nuclei counts in all rezafungin-treated groups compared to the vehicle control, except at the lowest and least frequently administered dose (0.2 mg/kg 1×/week). Three of the rezafungin groups—both 20-mg/kg regimens (20 mg/kg 1× or 3×/week) and the 2-mg/kg regimen (3×/week)—were comparable to the active control SXT, with no trophic nuclei microscopically detected (Fig. 3a). Similarly, asci counts in all rezafungin-treated groups were significantly reduced compared to the vehicle control. The efficacy observed in all but the 0.2-mg/kg 1×/week dose group was comparable to that of SXT, with no asci microscopically detected (Fig. 3b).

FIG 3
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FIG 3

Clearance and significant decreases in kidney burden of Pneumocystis (P. murina; both trophic [a] and asci [b] forms) in mice after administration of rezafungin prophylaxis compared to active control SXT. *, P < 0.05 versus the control. The limit of microscopic observation on this scale is log10 of 4 (the value indicating that no nuclei or asci were observed).

DISCUSSION

In this series of in vivo experiments, the novel echinocandin rezafungin was efficacious in preventing infection caused by Candida, Aspergillus, and Pneumocystis in immunosuppressed mice. Although the interpretation of these findings is limited to the extent that preclinical research may translate to clinical experience, the clinical efficacy demonstrated by currently available, once-daily echinocandins against all three of the fungal pathogens studied supports the predictive value of these in vivo data. The role of preclinical models notwithstanding, these results contribute to the development of rezafungin and the future of antifungal prophylaxis for patients at risk for IFD. To our knowledge, rezafungin is the first echinocandin to report prophylactic efficacy against Pneumocystis, as well as against Candida and Aspergillus.

Safe and efficacious antifungal prophylaxis is important and yet increasingly challenging to provide in a growing number of immunosuppressed conditions and patient populations at risk of developing IFD. The current mainstays of prophylaxis against these key pathogens (azoles and SXT) are generally efficacious but limited by DDIs and/or toxicity that can impede prophylaxis, as well as the treatment of primary disease (39, 40). Alternative therapies for prophylaxis are lacking. Pentamidine, dapsone, and atovaquone, as options for PCP prophylaxis, each have tolerability issues, limitations in efficacy, or administration challenges in the case of inhaled pentamidine (41). Liposomal amphotericin B at intermittent or low doses has been used for prophylaxis of Candida and Aspergillus but is hampered by a side-effect profile that includes nephrotoxicity and electrolyte abnormalities. In contrast, the relative tolerability and lack of DDIs with echinocandins present an attractive safety profile (41, 42). While all three echinocandins have been studied in various patient populations (13, 43–48), only micafungin is indicated for use as antifungal prophylaxis, specifically, of Candida infections in adult and pediatric patients undergoing hematopoietic stem cell transplantation (12, 49, 50). In a retrospective study in patients with hematological disease who received antifungal prophylaxis, micafungin was selected in 26% of 104 cases for safety- or tolerability-related reasons (e.g., liver dysfunctions, severe mucositis, DDIs of other antifungals, and long QT syndrome) (51). The safety of rezafungin is consistent with that of the echinocandin class, as observed in the phase 2 STRIVE trial of once-weekly rezafungin compared to caspofungin in the treatment of candidemia and invasive candidiasis (35, 52) and in phase 1 trials that confirmed rezafungin lack of effect on the QT interval and low DDI potential (37, 38).

The efficacy findings reported here also underscore the distinctive pharmacokinetics of rezafungin. Its long half-life and front-loaded drug exposure allow for once-weekly dosing of rezafungin, as studied in the completed phase 2 and ongoing phase 3 clinical trials. Furthermore, rezafungin demonstrates extensive distribution and tissue penetration, as shown by Zhao et al. (53), who observed 4-fold-higher rezafungin concentrations within lesions than for micafungin at the same dosage in a mouse intra-abdominal abscess model. Rezafungin is distributed to lung epithelial lining fluid and has demonstrated high in vivo exposures in the lung and other organs commonly infected by IFD, ∼4-fold higher than in plasma (54–56). These pharmacokinetics, together with the in vivo efficacy of rezafungin demonstrated here, suggest a potential to replace poorly tolerated combination regimens for prophylaxis in patients at risk for IFD, many of whom are burdened by polypharmacy and increasingly longer periods of infection risk.

The current set of in vivo studies on rezafungin contribute important findings to the published literature on this novel echinocandin and on approaches to antifungal prophylaxis. The efficacy of rezafungin in preventing infections caused by Candida, Aspergillus, and Pneumocystis in immunosuppressed mice demonstrate the potential of rezafungin as prophylaxis for patients at high risk of infection and support its ongoing clinical development.

MATERIALS AND METHODS

These studies were performed in accordance with the Guide for the Care and Use of Laboratory Animals, 8th ed. (National Academies Press, Washington, DC), in AAALAC-accredited ABSL-2 laboratories (with the exception of P. murina-infected mice) under the supervision of veterinarians. In addition, all procedures were conducted in compliance with the Institutional Animal Care and Use Committee at the respective sites.

Test agents were supplied by Cidara Therapeutics, Inc. (San Diego, CA), except for SXT (Sulfatrim H pediatric oral suspension; Actavis, Baltimore, MD), and amphotericin B (Sigma), which were purchased.

Invasive candidiasis prophylaxis mouse model.Female ICR mice (Envigo Laboratories) weighing ∼0.02 kg were immunosuppressed using two intraperitoneal (i.p.) injections of cyclophosphamide, with a first injection of 150 mg/kg administered 4 days before challenge (day −4) with Candida albicans (American Type Culture Collection [ATCC] SC5314; Manassas, VA; 4.5 log10 CFU/mouse intravenous [i.v.]) and a second injection of 100 mg/kg administered 1 day before challenge (day −1). Prior to C. albicans challenge, mice (n = 5/group; 9 groups) were treated with one subcutaneous (s.c.) dose of either rezafungin 5, 10, or 20 mg/kg on either day −5 (which is similar to day −15 for humans, based on a 2- to 3-fold faster clearance in mice), day −3, or day −1. In three additional groups, mice were given either rezafungin at 5 mg/kg s.c., micafungin at 5 mg/kg i.p., or s.c. vehicle control on day 0 administered immediately following C. albicans challenge. Treated mice were sacrificed at 24 h postchallenge, and the kidneys were harvested for bioburden enumeration (CFU/g of tissue).

Invasive aspergillosis prophylaxis mouse model.Female ICR mice (BioLasco Taiwan/Charles River) weighing ∼0.02 kg were immunosuppressed using three i.p. injections of cyclophosphamide, with the first injection (6 mg/mouse) administered 3 days before challenge (day –3) with Aspergillus fumigatus (ATCC 13073; Rockville, MD; 1.85 × 104 CFU/mouse i.v.) and the second and third injections (2 mg/mouse) administered 1 day before (day –1) and 4 days after (day 4) challenge. Prior to A. fumigatus challenge, mice (n = 6/group; 9 groups) were treated with one s.c. rezafungin dose of either 5, 10, or 20 mg/kg on either day −5 (similar to day −15 for humans as noted above, day −3, or day −1. In two additional groups, mice were given either rezafungin at 5 mg/kg s.c. or amphotericin B at 3 mg/kg i.p. on day 0 administered 1 h after challenge with A. fumigatus. Mortality was observed for 14 days.

PCP prophylaxis mouse model.Male C3H/H3N mice (Charles River) weighing ∼0.02 kg were immunosuppressed using dexamethasone (4 mg/liter) added to drinking water acidified with sulfuric acid (1 ml/liter) to prevent secondary microbial infections. Prophylaxis was administered at the same time as inoculation with Pneumocystis murina (Cincinnati VAMC Veterinary Medical Unit, Cincinnati, OH; 2 × 106/50 µl intranasally), the standard for this Pneumocystis infection model, given the slower growth of Pneumocystis relative to other fungi. Eight groups of mice (n = 10/group) received either negative control (control steroid, no treatment), positive control (SXT at 50/250 mg/kg 3×/week i.p.), or rezafungin (0.2, 2, or 20 mg/kg i.p. 1× or 3×/week) for 6 weeks. Mice were sacrificed after 6 weeks, and the lungs were prepared for fungal count measurement (CFU/g of tissue) of both trophic and asci (cyst) forms by rapid Wright-Giemsa and cresyl echt violet stains, respectively (57).

Statistical analysis.Statistical analyses were conducted according to the respective study protocols as follows. In the study of invasive candidiasis, CFU counts for each mouse were log transformed, and P values were calculated in Microsoft Excel by using a two-sample Student t test assuming unequal variance with comparisons made between treatment groups and the 24-h vehicle control group. In the study of invasive aspergillosis, a Fisher exact test (two tailed) was conducted on the survival curves. In the study of Pneumocystis prophylaxis, nuclei and asci counts for each lung were log transformed and analyzed by analysis of variance. Individual groups were compared by using Dunn’s test for multiple comparisons (GraphPad Prism, v6).

ACKNOWLEDGMENTS

Animal experiments were conducted by teams at Pharmacology Discovery Services (Taipei, Taiwan), the University of Cincinnati College of Medicine (Cincinnati, OH), and Transpharm Preclinical Solutions (Jackson, MI) in compliance with each institute’s IACUC regulations and in general accordance with the Guide for the Care and Use of Laboratory Animals, 8th ed. (National Academies Press, Washington, DC) to ensure humane treatment of laboratory animals.

Medical writing assistance was provided by T. Chung (Scribant Medical) with funding by Cidara Therapeutics, Inc.

These experiments were funded by Cidara Therapeutics (San Diego, CA). The Pneumocystis-related experiments were also supported by the Cincinnati VAMC and Veterinary Medical Unit, Cincinnati, OH. Cidara Therapeutics had a role in the study design and decision to submit for publication. The funder did not have a role in data collection and interpretation.

Author disclosures of financial or other relationships relevant to the study were as follows: L.M. (none to disclose), M.T.C. (none to disclose), S.R.L. (none to disclose), and V.O. (employee and owner of stock/stock options, Cidara Therapeutics).

FOOTNOTES

    • Received 17 September 2020.
    • Returned for modification 31 October 2020.
    • Accepted 7 December 2020.
    • Accepted manuscript posted online 14 December 2020.
  • Copyright © 2021 Miesel et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

REFERENCES

  1. 1.↵
    1. Drgona L,
    2. Khachatryan A,
    3. Stephens J,
    4. Charbonneau C,
    5. Kantecki M,
    6. Haider S,
    7. Barnes R
    . 2014. Clinical and economic burden of invasive fungal diseases in Europe: focus on pre-emptive and empirical treatment of Aspergillus and Candida species. Eur J Clin Microbiol Infect Dis 33:7–21. doi:10.1007/s10096-013-1944-3.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Marr KA
    . 2008. Primary antifungal prophylaxis in hematopoietic stem cell transplant recipients: clinical implications of recent studies. Curr Opin Infect Dis 21:409–414. doi:10.1097/QCO.0b013e328307c7d9.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Cornely OA,
    2. Kontoyiannis DP
    . 2018. How to prophylax against invasive fungal infections in adult ALL? An unmet need. Mycoses 61:646–649. doi:10.1111/myc.12786.
    OpenUrlCrossRef
  4. 4.↵
    1. Aslam S,
    2. Rotstein C
    , AST Infectious Disease Community of Practice. 2019. Candida infections in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 33:e13623. doi:10.1111/ctr.13623.
    OpenUrlCrossRef
  5. 5.↵
    1. Fishman JA,
    2. Gans H
    , AST Infectious Diseases Community of Practice. 2019. Pneumocystis jiroveci in solid organ transplantation: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 33:e13587. doi:10.1111/ctr.13587.
    OpenUrlCrossRef
  6. 6.↵
    1. Husain S,
    2. Camargo JF
    . 2019. Invasive aspergillosis in solid-organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 33:e13544. doi:10.1111/ctr.13544.
    OpenUrlCrossRef
  7. 7.↵
    1. Freifeld AG,
    2. Bow EJ,
    3. Sepkowitz KA,
    4. Boeckh MJ,
    5. Ito JI,
    6. Mullen CA,
    7. Raad II,
    8. Rolston KV,
    9. Young JA,
    10. Wingard JR
    , Infectious Diseases Society of America. 2011. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 52:427–431. doi:10.1093/cid/ciq147.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    1. Maertens J,
    2. Cesaro S,
    3. Maschmeyer G,
    4. Einsele H,
    5. Donnelly JP,
    6. Alanio A,
    7. Hauser PM,
    8. Lagrou K,
    9. Melchers WJ,
    10. Helweg-Larsen J,
    11. Matos O,
    12. Bretagne S,
    13. Cordonnier C
    , 5th European Conference on Infections in Leukaemia (ECIL-5), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the Immunocompromised Host Society (ICHS), and the European LeukemiaNet (ELN). 2016. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients. J Antimicrob Chemother 71:2397–2404. doi:10.1093/jac/dkw157.
    OpenUrlCrossRefPubMed
  9. 9.↵
    1. Ullmann AJ,
    2. Aguado JM,
    3. Arikan-Akdagli S,
    4. Denning DW,
    5. Groll AH,
    6. Lagrou K,
    7. Lass-Florl C,
    8. Lewis RE,
    9. Munoz P,
    10. Verweij PE,
    11. Warris A,
    12. Ader F,
    13. Akova M,
    14. Arendrup MC,
    15. Barnes RA,
    16. Beigelman-Aubry C,
    17. Blot S,
    18. Bouza E,
    19. Bruggemann RJM,
    20. Buchheidt D,
    21. Cadranel J,
    22. Castagnola E,
    23. Chakrabarti A,
    24. Cuenca-Estrella M,
    25. Dimopoulos G,
    26. Fortun J,
    27. Gangneux JP,
    28. Garbino J,
    29. Heinz WJ,
    30. Herbrecht R,
    31. Heussel CP,
    32. Kibbler CC,
    33. Klimko N,
    34. Kullberg BJ,
    35. Lange C,
    36. Lehrnbecher T,
    37. Loffler J,
    38. Lortholary O,
    39. Maertens J,
    40. Marchetti O,
    41. Meis JF,
    42. Pagano L,
    43. Ribaud P,
    44. Richardson M,
    45. Roilides E,
    46. Ruhnke M,
    47. Sanguinetti M,
    48. Sheppard DC,
    49. Sinko J,
    50. Skiada A
    , et al. 2018. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 24(Suppl 1):e1–e38. doi:10.1016/j.cmi.2018.01.002.
    OpenUrlCrossRef
  10. 10.↵
    1. Baden LR,
    2. Swaminathan S,
    3. Angarone M,
    4. Blouin G,
    5. Camins BC,
    6. Casper C,
    7. Cooper B,
    8. Dubberke ER,
    9. Engemann AM,
    10. Freifeld AG,
    11. Greene JN,
    12. Ito JI,
    13. Kaul DR,
    14. Lustberg ME,
    15. Montoya JG,
    16. Rolston K,
    17. Satyanarayana G,
    18. Segal B,
    19. Seo SK,
    20. Shoham S,
    21. Taplitz R,
    22. Topal J,
    23. Wilson JW,
    24. Hoffmann KG,
    25. Smith C
    . 2016. Prevention and treatment of cancer-related infections, version 2.2016, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 14:882–913. doi:10.6004/jnccn.2016.0093.
    OpenUrlCrossRef
  11. 11.↵
    1. Ullmann AJ,
    2. Schmidt-Hieber M,
    3. Bertz H,
    4. Heinz WJ,
    5. Kiehl M,
    6. Kruger W,
    7. Mousset S,
    8. Neuburger S,
    9. Neumann S,
    10. Penack O,
    11. Silling G,
    12. Vehreschild JJ,
    13. Einsele H,
    14. Maschmeyer G
    , Infectious Diseases Working Party of the German Society for Hematology and Medical Oncology (AGIHO/DGHO) and the DAG-KBT (German Working Group for Blood and Marrow Transplantation). 2016. Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016. Ann Hematol 95:1435–1455. doi:10.1007/s00277-016-2711-1.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Epstein DJ,
    2. Seo SK,
    3. Huang YT,
    4. Park JH,
    5. Klimek VM,
    6. Berman E,
    7. Tallman MS,
    8. Frattini MG,
    9. Papanicolaou GA
    . 2018. Micafungin versus posaconazole prophylaxis in acute leukemia or myelodysplastic syndrome: a randomized study. J Infect 77:227–234. doi:10.1016/j.jinf.2018.03.015.
    OpenUrlCrossRef
  13. 13.↵
    1. Fisher BT,
    2. Zaoutis T,
    3. Dvorak CC,
    4. Nieder M,
    5. Zerr D,
    6. Wingard JR,
    7. Callahan C,
    8. Villaluna D,
    9. Chen L,
    10. Dang H,
    11. Esbenshade AJ,
    12. Alexander S,
    13. Wiley JM,
    14. Sung L
    . 2019. Effect of caspofungin versus fluconazole prophylaxis on invasive fungal disease among children and young adults with acute myeloid leukemia: a randomized clinical trial. JAMA 322:1673–1681. doi:10.1001/jama.2019.15702.
    OpenUrlCrossRef
  14. 14.↵
    1. Winston DJ,
    2. Bartoni K,
    3. Territo MC,
    4. Schiller GJ
    . 2011. Efficacy, safety, and breakthrough infections associated with standard long-term posaconazole antifungal prophylaxis in allogeneic stem cell transplantation recipients. Biol Blood Marrow Transpl 17:507–515. doi:10.1016/j.bbmt.2010.04.017.
    OpenUrlCrossRefPubMedWeb of Science
  15. 15.↵
    1. Kohl V,
    2. Müller C,
    3. Cornely OA,
    4. Abduljalil K,
    5. Fuhr U,
    6. Vehreschild JJ,
    7. Scheid C,
    8. Hallek M,
    9. Rüping MJGT
    . 2010. Factors influencing pharmacokinetics of prophylactic posaconazole in patients undergoing allogeneic stem cell transplantation. Antimicrob Agents Chemother 54:207–212. doi:10.1128/AAC.01027-09.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Lindsay J,
    2. Teh BW,
    3. Micklethwaite K,
    4. Slavin M
    . 2019. Azole antifungals and new targeted therapies for hematological malignancy. Curr Opin Infect Dis 32:538–545. doi:10.1097/QCO.0000000000000611.
    OpenUrlCrossRef
  17. 17.↵
    1. Maschmeyer G,
    2. De Greef J,
    3. Mellinghoff SC,
    4. Nosari A,
    5. Thiebaut-Bertrand A,
    6. Bergeron A,
    7. Franquet T,
    8. Blijlevens NMA,
    9. Maertens JA
    , European Conference on Infections in Leukemia (ECIL). 2019. Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology: a position paper by the European Conference on Infections in Leukemia (ECIL). Leukemia 33:844–862. doi:10.1038/s41375-019-0388-x.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Reinwald M,
    2. Silva JT,
    3. Mueller NJ,
    4. Fortun J,
    5. Garzoni C,
    6. de Fijter JW,
    7. Fernandez-Ruiz M,
    8. Grossi P,
    9. Aguado JM
    . 2018. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors). Clin Microbiol Infect 24(Suppl 2):S53–S70. doi:10.1016/j.cmi.2018.02.009.
    OpenUrlCrossRef
  19. 19.↵
    1. Chamilos G,
    2. Lionakis MS,
    3. Kontoyiannis DP
    . 2018. Call for action: invasive fungal infections associated with ibrutinib and other small molecule kinase inhibitors targeting immune signaling pathways. Clin Infect Dis doi:10.1093/cid/cix687.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Los-Arcos I,
    2. Aguilar-Company J,
    3. Ruiz-Camps I
    . 2019. Risk of infection associated with new therapies for the treatment of lymphoproliferative syndromes. Med Clin (Barc) 154:101–107. doi:10.1016/j.medcli.2019.07.026.
    OpenUrlCrossRef
  21. 21.↵
    1. Varughese T,
    2. Taur Y,
    3. Cohen N,
    4. Palomba ML,
    5. Seo SK,
    6. Hohl TM,
    7. Redelman-Sidi G
    . 2018. Serious infections in patients receiving ibrutinib for treatment of lymphoid cancer. Clin Infect Dis 67–692. doi:10.1093/cid/ciy175.
    OpenUrlCrossRef
  22. 22.↵
    1. Butts A,
    2. Reitler P,
    3. Ge W,
    4. Fortwendel JR,
    5. Palmer GE
    . 2018. Commonly used oncology drugs decrease antifungal effectiveness against Candida and Aspergillus species. Antimicrob Agents Chemother 62:e00504-18. doi:10.1128/AAC.00504-18.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Del Castillo M,
    2. Romero FA,
    3. Arguello E,
    4. Kyi C,
    5. Postow MA,
    6. Redelman-Sidi G
    . 2016. The spectrum of serious infections among patients receiving immune checkpoint blockade for the treatment of melanoma. Clin Infect Dis 63:1490–1493. doi:10.1093/cid/ciw539.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Kyi C,
    2. Hellmann MD,
    3. Wolchok JD,
    4. Chapman PB,
    5. Postow MA
    . 2014. Opportunistic infections in patients treated with immunotherapy for cancer. J Immunother Cancer 2:19–19. doi:10.1186/2051-1426-2-19.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Brahmer JR,
    2. Lacchetti C,
    3. Schneider BJ,
    4. Atkins MB,
    5. Brassil KJ,
    6. Caterino JM,
    7. Chau I,
    8. Ernstoff MS,
    9. Gardner JM,
    10. Ginex P,
    11. Hallmeyer S,
    12. Holter Chakrabarty J,
    13. Leighl NB,
    14. Mammen JS,
    15. McDermott DF,
    16. Naing A,
    17. Nastoupil LJ,
    18. Phillips T,
    19. Porter LD,
    20. Puzanov I,
    21. Reichner CA,
    22. Santomasso BD,
    23. Seigel C,
    24. Spira A,
    25. Suarez-Almazor ME,
    26. Wang Y,
    27. Weber JS,
    28. Wolchok JD,
    29. Thompson JA
    , National Comprehensive Cancer Network. 2018. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 36:1714–1768. doi:10.1200/JCO.2017.77.6385.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Redelman-Sidi G,
    2. Michielin O,
    3. Cervera C,
    4. Ribi C,
    5. Aguado JM,
    6. Fernandez-Ruiz M,
    7. Manuel O
    . 2018. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective (immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors). Clin Microbiol Infect 24(Suppl 2):S95–S107. doi:10.1016/j.cmi.2018.01.030.
    OpenUrlCrossRef
  27. 27.↵
    1. Toth Z,
    2. Forgacs L,
    3. Locke JB,
    4. Kardos G,
    5. Nagy F,
    6. Kovacs R,
    7. Szekely A,
    8. Borman AM,
    9. Majoros L
    . 2019. In vitro activity of rezafungin against common and rare Candida species and Saccharomyces cerevisiae. J Antimicrob Chemother 74:3505–3510. doi:10.1093/jac/dkz390.
    OpenUrlCrossRef
  28. 28.↵
    1. Pfaller MA,
    2. Messer SA,
    3. Rhomberg PR,
    4. Castanheira M
    . 2017. Activity of a long-acting echinocandin (CD101) and seven comparator antifungal agents tested against a global collection of contemporary invasive fungal isolates in the SENTRY 2014. Antimicrob Agents Chemother 61:e02045-16. doi:10.1128/AAC.02045-16.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    1. Pfaller MA,
    2. Messer SA,
    3. Rhomberg PR,
    4. Castanheira M
    . 2017. CD101, a long-acting echinocandin, and comparator antifungal agents tested against a global collection of invasive fungal isolates in the SENTRY 2015 Antifungal Surveillance Program. Int J Antimicrob Agents 50:352–358. doi:10.1016/j.ijantimicag.2017.03.028.
    OpenUrlCrossRef
  30. 30.↵
    1. Berkow EL,
    2. Lockhart SR
    . 2018. Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris. Diagn Microbiol Infect Dis 90:196–197. doi:10.1016/j.diagmicrobio.2017.10.021.
    OpenUrlCrossRef
  31. 31.↵
    1. Pfaller MA,
    2. Messer SA,
    3. Rhomberg PR,
    4. Jones RN,
    5. Castanheira M
    . 2016. Activity of a long-acting echinocandin, CD101, determined using CLSI and EUCAST reference methods, against Candida and Aspergillus spp., including echinocandin- and azole-resistant isolates. J Antimicrob Chemother 71:2868–2873. doi:10.1093/jac/dkw214.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Wiederhold NP,
    2. Najvar LK,
    3. Jaramillo R,
    4. Olivo M,
    5. Wickes BL,
    6. Catano G,
    7. Patterson TF
    . 2019. Extended-interval dosing of rezafungin against azole-resistant Aspergillus fumigatus. Antimicrob Agents Chemother 63:e01165-19. doi:10.1128/AAC.01165-19.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    1. Wiederhold NP,
    2. Locke JB,
    3. Daruwala P,
    4. Bartizal K
    . 2020. Rezafungin (CD101) demonstrates potent in vitro activity against Aspergillus, including azole-resistant Aspergillus fumigatus isolates and cryptic species. J Antimicrob Chemother 73:3063–3067. doi:10.1093/jac/dky280.
    OpenUrlCrossRef
  34. 34.↵
    1. Cushion MT,
    2. Locke JB,
    3. Ong V,
    4. Bartizal K
    . 2018. Novel once-weekly echinocandin rezafungin (CD101) prevention and treatment of pneumocystis biofilms, abstr. EBMT, Lisbon, Portugal.
  35. 35.↵
    1. Ong V,
    2. Hough G,
    3. Schlosser M,
    4. Bartizal K,
    5. Balkovec JM,
    6. James KD,
    7. Krishnan BR
    . 2016. Preclinical evaluation of the stability, safety, and efficacy of CD101, a novel echinocandin. Antimicrob Agents Chemother 61:e00701-16. doi:10.1128/AAC.00701-16.
    OpenUrlAbstract/FREE Full Text
  36. 36.↵
    1. Sandison T,
    2. Ong V,
    3. Lee J,
    4. Thye D
    . 2017. Safety and pharmacokinetics of CD101 IV, a novel echinocandin, in healthy adults. Antimicrob Agents Chemother 61:e01627-16. doi:10.1128/AAC.01627-16.
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Flanagan S,
    2. Goodman DB,
    3. Jandourek A,
    4. O’Reilly T,
    5. Sandison T
    . 2019. Lack of effect of rezafungin on QT/QTc interval in healthy subjects. Clin Pharmacol Drug Dev 9:456–465. doi:10.1002/cpdd.757.
    OpenUrlCrossRef
  38. 38.↵
    1. Ong V,
    2. Sandison T,
    3. Flanagan S
    . 2019. No relevant pharmacokinetic (PK) interaction between rezafungin and nine probe drugs: results from a drug-drug interaction (DDI) study. Biol Blood Marrow Transpl 25:S357. doi:10.1016/j.bbmt.2018.12.579.
    OpenUrlCrossRef
  39. 39.↵
    1. Moriyama B,
    2. Henning SA,
    3. Leung J,
    4. Falade-Nwulia O,
    5. Jarosinski P,
    6. Penzak SR,
    7. Walsh TJ
    . 2012. Adverse interactions between antifungal azoles and vincristine: review and analysis of cases. Mycoses 55:290–297. doi:10.1111/j.1439-0507.2011.02158.x.
    OpenUrlCrossRefPubMed
  40. 40.↵
    1. Agarwal SK,
    2. DiNardo CD,
    3. Potluri J,
    4. Dunbar M,
    5. Kantarjian HM,
    6. Humerickhouse RA,
    7. Wong SL,
    8. Menon RM,
    9. Konopleva MY,
    10. Salem AH
    . 2017. Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin Ther 39:359–367. doi:10.1016/j.clinthera.2017.01.003.
    OpenUrlCrossRef
  41. 41.↵
    1. Epstein D,
    2. Seo SK,
    3. Brown JM,
    4. Papanicolaou G
    . 2017. Echinocandin prophylaxis in patients undergoing hematopoietic cell transplantation and other treatments for hematologic malignancies. J Antimicrob Chemother 73(Suppl 1):i60–i72. doi:10.1093/jac/dkx450.
    OpenUrlCrossRef
  42. 42.↵
    1. Niwa T,
    2. Imagawa Y,
    3. Yamazaki H
    . 2014. Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr Drug Metab 15:651–679. doi:10.2174/1389200215666141125121511.
    OpenUrlCrossRefPubMed
  43. 43.↵
    1. Cattaneo C,
    2. Monte S,
    3. Algarotti A,
    4. Audisio E,
    5. Borlenghi E,
    6. Campiotti L,
    7. Cerqui E,
    8. Fanizza C,
    9. Giuliani R,
    10. Mico C,
    11. Rocconi R,
    12. Salvi A,
    13. Salvi F,
    14. Verga L,
    15. Levis A,
    16. Lambertenghi Deliliers G,
    17. Pogliani EM,
    18. Tognoni G,
    19. Rambaldi A,
    20. Rossi G
    . 2011. A randomized comparison of caspofungin versus antifungal prophylaxis according to investigator policy in acute leukaemia patients undergoing induction chemotherapy (PROFIL-C study). J Antimicrob Chemother 66:2140–2145. doi:10.1093/jac/dkr271.
    OpenUrlCrossRefPubMed
  44. 44.↵
    1. Mattiuzzi GN,
    2. Alvarado G,
    3. Giles FJ,
    4. Ostrosky-Zeichner L,
    5. Cortes J,
    6. O’Brien S,
    7. Verstovsek S,
    8. Faderl S,
    9. Zhou X,
    10. Raad II,
    11. Bekele BN,
    12. Leitz GJ,
    13. Lopez-Roman I,
    14. Estey EH
    . 2006. Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies. Antimicrob Agents Chemother 50:143–147. doi:10.1128/AAC.50.1.143-147.2006.
    OpenUrlAbstract/FREE Full Text
  45. 45.↵
    1. Ostrosky-Zeichner L,
    2. Shoham S,
    3. Vazquez J,
    4. Reboli A,
    5. Betts R,
    6. Barron MA,
    7. Schuster M,
    8. Judson MA,
    9. Revankar SG,
    10. Caeiro JP,
    11. Mangino JE,
    12. Mushatt D,
    13. Bedimo R,
    14. Freifeld A,
    15. Nguyen MH,
    16. Kauffman CA,
    17. Dismukes WE,
    18. Westfall AO,
    19. Deerman JB,
    20. Wood C,
    21. Sobel JD,
    22. Pappas PG
    . 2014. MSG-01: a randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting. Clin Infect Dis 58:1219–1226. doi:10.1093/cid/ciu074.
    OpenUrlCrossRefPubMed
  46. 46.↵
    1. Saliba F,
    2. Pascher A,
    3. Cointault O,
    4. Laterre PF,
    5. Cervera C,
    6. De Waele JJ,
    7. Cillo U,
    8. Langer RM,
    9. Lugano M,
    10. Goran-Ericzon B,
    11. Phillips S,
    12. Tweddle L,
    13. Karas A,
    14. Brown M,
    15. Fischer L
    , TENPIN Liver Transplant European Study Into the Prevention of Fungal Infection Investigators. 2015. Randomized trial of micafungin for the prevention of invasive fungal infection in high-risk liver transplant recipients. Clin Infect Dis 60:997–1006. doi:10.1093/cid/ciu1128.
    OpenUrlCrossRefPubMed
  47. 47.↵
    1. Bruggemann RJ,
    2. Van Der Velden WJ,
    3. Knibbe CA,
    4. Colbers A,
    5. Hol S,
    6. Burger DM,
    7. Donnelly JP,
    8. Blijlevens NM
    . 2015. A rationale for reduced-frequency dosing of anidulafungin for antifungal prophylaxis in immunocompromised patients. J Antimicrob Chemother 70:1166–1174. doi:10.1093/jac/dku477.
    OpenUrlCrossRefPubMed
  48. 48.↵
    1. Winston DJ,
    2. Limaye AP,
    3. Pelletier S,
    4. Safdar N,
    5. Morris MI,
    6. Meneses K,
    7. Busuttil RW,
    8. Singh N
    . 2014. Randomized, double-blind trial of anidulafungin versus fluconazole for prophylaxis of invasive fungal infections in high-risk liver transplant recipients. Am J Transplant 14:2758–2764. doi:10.1111/ajt.12963.
    OpenUrlCrossRefPubMed
  49. 49.↵
    Astellas Pharma US. 2019. Mycamine (micafungin sodium). Package insert. Astellas Pharma US, Inc, Northbrook, IL.
  50. 50.↵
    1. El-Cheikh J,
    2. Venton G,
    3. Crocchiolo R,
    4. Fürst S,
    5. Faucher C,
    6. Granata A,
    7. Oudin C,
    8. Coso D,
    9. Bouabdallah R,
    10. Vey N,
    11. Duran S,
    12. Fougereau E,
    13. Berger P,
    14. Chabannon C,
    15. Blaise D
    . 2013. Efficacy and safety of micafungin for prophylaxis of invasive fungal infections in patients undergoing haplo-identical hematopoietic SCT. Bone Marrow Transplant 48:1472–1477. doi:10.1038/bmt.2013.87.
    OpenUrlCrossRefPubMed
  51. 51.↵
    1. Villaescusa T,
    2. Vazquez L,
    3. Bergua JM,
    4. Garcia J,
    5. Romero A,
    6. Olave MT,
    7. Garcia Belmonte D,
    8. Queipo de Llano MP
    , Hospital Virgen de la Concha. 2020. Micafungin as antifungal prophylaxis in non-transplanted haemotological patients. Rev Esp Quimioter 33:44–48. doi:10.37201/req/067.2019.
    OpenUrlCrossRef
  52. 52.↵
    1. Thompson GR, III,
    2. Soriano A,
    3. Skoutelis A,
    4. Vazquez JA,
    5. Honore PM,
    6. Horcajada JP,
    7. Spapen H,
    8. Bassetti M,
    9. Ostrosky-Zeichner L,
    10. Das AF,
    11. Viani RM,
    12. Sandison T,
    13. Pappas PG
    . 2020. Rezafungin versus caspofungin in a phase 2, randomized, double-blind study for the treatment of candidemia and invasive candidiasis—the STRIVE trial. Clin Infect Dis ciaa1380. doi:10.1093/cid/ciaa1380.
    OpenUrlCrossRef
  53. 53.↵
    1. Zhao Y,
    2. Prideaux B,
    3. Nagasaki Y,
    4. Lee MH,
    5. Chen PY,
    6. Blanc L,
    7. Ho H,
    8. Clancy CJ,
    9. Nguyen MH,
    10. Dartois V,
    11. Perlin DS
    . 2017. Unraveling drug penetration of echinocandin antifungals at the site of infection in an intra-abdominal abscess model. Antimicrob Agents Chemother 61:e01009–17. doi:10.1128/AAC.01009-17.
    OpenUrlAbstract/FREE Full Text
  54. 54.↵
    1. Brown JM,
    2. Lakota EA,
    3. Flanagan S,
    4. Sandison T,
    5. Ong V,
    6. Rubino CM
    . 2019. Pharmacokinetic-pharmacodynamic analyses of dose selection for rezafungin prophylaxis against invasive fungal infections in bone marrow transplantation. Biol Blood Marrow Transpl 25:S358–S359. doi:10.1016/j.bbmt.2018.12.581.
    OpenUrlCrossRef
  55. 55.↵
    1. Ong V,
    2. Flanagan S,
    3. Sandison T,
    4. Bartizal K,
    5. Satta A,
    6. Sharp A,
    7. Thommes P,
    8. Murphy T
    . 2018. CD101 lung epithelial lining fluid (ELF) concentrations substantiate its use for prophylaxis treatment as evident in mouse disseminated and pulmonary aspergillosis models, abstr. Advances against Aspergillosis, Lisbon, Portugal.
  56. 56.↵
    1. Ong V,
    2. James KD,
    3. Smith S,
    4. Krishnan BR
    . 2017. Pharmacokinetics of the novel echinocandin CD101 in multiple animal species. Antimicrob Agents Chemother 61:e01626-16. doi:10.1128/AAC.01626-16.
    OpenUrlAbstract/FREE Full Text
  57. 57.↵
    1. Cushion MT,
    2. Linke MJ,
    3. Ashbaugh A,
    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.
    OpenUrlCrossRefPubMed
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Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia
Lynn Miesel, Melanie T. Cushion, Alan Ashbaugh, Santiago R. Lopez, Voon Ong
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01992-20; DOI: 10.1128/AAC.01992-20

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Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia
Lynn Miesel, Melanie T. Cushion, Alan Ashbaugh, Santiago R. Lopez, Voon Ong
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01992-20; DOI: 10.1128/AAC.01992-20
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KEYWORDS

Aspergillus
Candida
Pneumocystis
antifungal agents
antifungal therapy
echinocandin
prophylaxis

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