Lessons from isavuconazole therapeutic drug monitoring at a United Kingdom Reference Center

Borman, Andrew M.; Hughes, Jessica M; Oliver, Debra; Fraser, Mark; Sunderland, J.; Noel, Alan; Johnson, Elizabeth

doi:10.1093/mmy/myaa022

Cited by 25 publications

(18 citation statements)

References 15 publications

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“…The clinical phase III trial SECURE found the majority of s-ISZ measurements were within the range of 1–7 mg/L [ 23 ]. The median value in the present study was 4.3 mg/L and well within that range, the same as in other studies [ 7 , 8 , 9 , 12 , 17 , 24 , 25 , 26 ]. In the present study, the majority of the s-ISZ measurements were also within the recommended range, but for VRZ a third of TDM measurements were outside the recommended range, which is also in accordance with the literature [ 27 ].…”

Section: Discussionsupporting

confidence: 92%

“…In the CPA population, mean CV intraindividual was 30% at a dosage of 100 mg and 20% at a dosage of 200 mg, suggesting that ISZ 100 mg might be adequate for CPA [ 14 ]. Others have reported ISZ CVs from 61.52% to 66% [ 24 , 26 ]. One of the studies found a higher ISZ CV in patients < 18 years [ 26 ], as we also did for VRZ in the pediatric group in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Others have reported ISZ CVs from 61.52% to 66% [ 24 , 26 ]. One of the studies found a higher ISZ CV in patients < 18 years [ 26 ], as we also did for VRZ in the pediatric group in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Limitations to this study are the retrospective design and the limited number of patients. Since many studies, including ours, are retrospective [ 12 , 17 , 24 , 26 ], there is no certainty that the included samples were trough samples. One prospective trial did however manage to include trough levels only and found a median s-ISZ of 2.35 mg/L [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

et al. 2021

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Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2–10 mg/L, but was adjusted to 2–5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5–15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2–21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug–drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

et al. 2021

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“…Moreover, the results of direct comparisons of the activity of these two triazoles in vitro are somewhat contradictory, with some studies showing roughly equivalent activities but species-specific variations [11,12], whilst others suggested that posaconazole MICs were generally lower than isavuconazole MICs with the common agents of mucoromycosis [13,14]. Additionally, it remains to be determined whether reported MIC differences between posaconazole and isavuconazole with members of the Mucorales are clinically relevant, given that drug exposures in vivo are usually higher with isavuconazole than with posaconazole [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Antifungal Drug Resistance Profiles of Clinically Relevant Members of the Mucorales (Mucoromycota) Especially with the Newer Triazoles

Borman

Fraser

Patterson

et al. 2021

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Mucoromycoses (infections caused by members of the order Mucorales, phylum Mucoromycota [ex-Zygomycota]) are highly destructive, rapidly progressive infections, with dire prognoses especially when they occur in immunocompromised hosts. Current treatment guidelines recommend liposomal formulations of amphotericin B with adjunctive surgery as first line therapy, with the newer triazoles posaconazole or isavuconazole as alternative treatments, or as salvage therapy. Among the many organisms belonging to this order, a limited number of species in the genera Rhizopus, Mucor, Lichtheimia and Rhizomucor are responsible for most cases of human infection. Here, we present the minimum inhibitory concentration data (MICs) for amphotericin B, posaconazole, isavuconazole, itraconazole and voriconazole with a panel of over 300 isolates of the five most common agents of human infection (Lichtheimia corymbifera, Rhizopus arrhizus, R. microsporus, Rhizomucor pusillus and Mucor spp.) determined using the CLSI broth microdilution method. In agreement with previous studies, the most active antifungal drug for all Mucorales was amphotericin B, with MICs within the range that would predict susceptibility with Aspergillus fumigatus. Conversely, MICs for voriconazole against all species tested were high, and above the range associated with clinical efficacy with A. fumigatus. Interestingly, whilst isavuconazole and posaconazole MIC distributions indicated in vitro activity against some members of the Mucorales, activity was species-dependent for both agents. These data underscore the importance of accurate identification of the causative agents of mucoromycosis, coupled with antifungal susceptibility testing of individual isolates, in determining the optimal treatment of infections caused by these aggressive opportunistic human fungal pathogens.

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Invasive Fungal Disease in Immunocompromised Children: Current and Emerging Therapies

Brophy-Williams,

Ewe,

Yeoh

2024

Curr Infect Dis Rep

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Lessons from isavuconazole therapeutic drug monitoring at a United Kingdom Reference Center

Cited by 25 publications

References 15 publications

Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

In Vitro Antifungal Drug Resistance Profiles of Clinically Relevant Members of the Mucorales (Mucoromycota) Especially with the Newer Triazoles

Invasive Fungal Disease in Immunocompromised Children: Current and Emerging Therapies

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