Successful treatment of<i>Aspergillus</i>ventriculitis through voriconazole adaptive pharmacotherapy, immunomodulation, and therapeutic monitoring of cerebrospinal fluid (1→3)-β-D-glucan

Chen, Tempe K.; Groncy, Paula K.; Javahery, Ramin J.; Chai, Richard Y.; Nagpala, Pablito G.; Finkelman, Malcolm; Petraitienė, Rūta; Walsh, Thomas J.

doi:10.1093/mmy/myw118

Cited by 29 publications

(18 citation statements)

References 27 publications

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“…Recapitulating the findings for the parameters of organism-mediated injury, survival, pulmonary fungal burden, and serial (1¡3)-␤-D-glucan levels, animals treated with ISA60 or ISA60-MFG2 also demonstrated resolution of the elevated GMI in serum. The validity of GMI in reflecting the therapeutic response is buttressed by previous studies with animal models of pulmonary aspergillosis (8,9,13,14) and patients with invasive aspergillosis (15)(16)(17)(18)(19)(20)(21).…”

Section: Figmentioning

confidence: 99%

Combination Therapy with Isavuconazole and Micafungin for Treatment of Experimental Invasive Pulmonary Aspergillosis

Petraitis

Petraitienė

McCarthy

et al. 2017

Antimicrob Agents Chemother

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Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity and mortality in immunocompromised patients. We hypothesized that simultaneous inhibition of biosynthesis of ergosterol in the fungal cell membrane and (1→3)-β-d-glucan in the cell wall, respectively, by the antifungal triazole isavuconazole (ISA) and the echinocandin micafungin (MFG) may result in improved outcomes in experimental IPA in persistently neutropenic rabbits. Treatments included ISA at 20 mg/kg of body weight/day (ISA20), 40 mg/kg/day (ISA40), and 60 mg/kg/day (ISA60); MFG at 2 mg/kg/day (MFG2); combinations of ISA20 and MFG2, ISA40 and MFG2, and ISA60 and MFG2; and no treatment (untreated controls [UC]). The galactomannan index (GMI) and (1→3)-β-d-glucan levels in serum were measured. The residual fungal burden (number of CFU per gram) was significantly reduced in ISA20-, ISA40-, ISA60-, ISA20-MFG2-, ISA40-MFG2-, and ISA60-MFG2-treated rabbits compared with that in MFG2-treated or UC rabbits ( < 0.01). Measures of organism-mediated pulmonary injury, lung weights, and pulmonary infarct score were lower in ISA40-MFG2-treated rabbits than in rabbits treated with ISA40 or MFG2 alone ( < 0.01). Survival was prolonged in ISA40-MFG2-treated rabbits in comparison to those treated with ISA40 or MFG2 alone ( < 0.01). These outcome variables correlated directly with significant declines in GMI and serum (1→3)-β-d-glucan levels during therapy. The GMI correlated with measures of organism-mediated pulmonary injury, lung weights ( = 0.764; < 0.001), and pulmonary infarct score ( = 0.911; < 0.001). In summary, rabbits receiving combination therapy with isavuconazole and micafungin demonstrated a significant dose-dependent reduction in the residual fungal burden, decreased pulmonary injury, prolonged survival, a lower GMI, and lower serum (1→3)-β-d-glucan levels in comparison to rabbits receiving isavuconazole or micafungin as a single agent.

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Section: Figmentioning

confidence: 99%

Combination Therapy with Isavuconazole and Micafungin for Treatment of Experimental Invasive Pulmonary Aspergillosis

Petraitis

Petraitienė

McCarthy

et al. 2017

Antimicrob Agents Chemother

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“…TDM‐guided long‐term voriconazole therapy was proved effective in the treatment of central nervous system (CNS) aspergillosis without occurrence of severe adverse events in two young patients who experienced postneurosurgical‐related infections (brain abscess aspergillosis and ventriculitis ).…”

Section: Discussionmentioning

confidence: 99%

Successful and safe long‐term treatment of cerebral aspergillosis with high‐dose voriconazole guided by therapeutic drug monitoring

Cojutti

Merelli

Allegri

et al. 2018

Brit J Clinical Pharma

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We report the case of a patient who had cerebral aspergillosis after otorhinolaryngologic surgery and who was successfully and safely treated with high‐dose voriconazole (200 mg q6h) for more than 1 year thanks to a TDM‐guided approach coupled with pharmacological review and with genotyping of CYP2C19 polymorphisms. The findings support the idea that personalized medicine based on TDM coupled with the need of avoiding drug–drug interactions may be helpful for maximizing the net benefit (probability of efficacy vs. probability of adverse events) of voriconazole in the management of long‐term treatment of cerebral aspergillosis.

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“…On an individual patient level, GM-CSF has shown promising results. Chen et al (2017) reported success where GM-CSF was used as adjunct therapy to treat Aspergillus ventriculitis. GM-CSF was given in conjunction with voriconazole, amphotericin B, and caspofungin.…”

Section: Cytokine Therapymentioning

confidence: 99%

Immunomodulation as Therapy for Fungal Infection: Are We Closer?

et al. 2018

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Invasive fungal disease (IFD) causes significant morbidity in immunocompromised patients due to their weakened immune system. Immunomodulatory therapy, in synergy with existing antifungal therapy, is an attractive option to enhance their immune system and aid clearance of these opportunistic pathogens. From a scientific and clinical perspective, we explore the immunotherapeutic options to augment standard antifungal drugs for patients with an IFD. We discuss the range of immunomodulatory therapies being considered in IFD – from cytokines, including G-CSF, GM-CSF, M-CSF, IFN-γ, and cytokine agonists, to cellular therapies, consisting of granulocyte transfusion, adoptive T-cell, CAR T-cell, natural killer cell therapies, and monoclonal antibodies. Adjunct pharmaceutical agents which augment the immunity are also being considered. Lastly, we explore the likelihood of the use of probiotics and manipulation of the microbiome/mycobiome to enhance IFD treatment outcomes.

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Successful treatment ofAspergillusventriculitis through voriconazole adaptive pharmacotherapy, immunomodulation, and therapeutic monitoring of cerebrospinal fluid (1→3)-β-D-glucan

Cited by 29 publications

References 27 publications

Combination Therapy with Isavuconazole and Micafungin for Treatment of Experimental Invasive Pulmonary Aspergillosis

Combination Therapy with Isavuconazole and Micafungin for Treatment of Experimental Invasive Pulmonary Aspergillosis

Successful and safe long‐term treatment of cerebral aspergillosis with high‐dose voriconazole guided by therapeutic drug monitoring

Immunomodulation as Therapy for Fungal Infection: Are We Closer?

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