Dataset Information

Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific.

ABSTRACT: Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017-2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC_50/90, 2/>8 mg/L) inhibited 59.6% and 71.2% of all Mucorales isolates at ≤2 mg/L and ≤4 mg/L, respectively. Among comparators, amphotericin B (MIC_50/90, 0.5/1 mg/L) displayed the highest activity, followed by posaconazole (MIC_50/90, 0.5/8 mg/L). Voriconazole (MIC_50/90, >8/>8 mg/L) and the echinocandins (MIC_50/90, >4/>4 mg/L) had limited activity against Mucorales isolates. Isavuconazole activity varied by species and this agent inhibited at ≤4 mg/L 85.2%, 72.7%, and 25% of Rhizopus spp. (n = 27; MIC_50/90, 1/>8 mg/L), Lichtheimia spp. (n = 11; MIC_50/90, 4/8 mg/L), and Mucor spp. (n = 8; MIC₅₀, >8 mg/L) isolates, respectively. Posaconazole MIC_50/90 values against Rhizopus, Lichtheimia, and Mucor species were 0.5/8 mg/L, 0.5/1 mg/L, and 2/- mg/L, respectively; amphotericin B MIC_50/90 values were 1/1 mg/L, 0.5/1 mg/L, and 0.5/- mg/L, respectively. As susceptibility profiles varied among Mucorales genera, species identification and antifungal susceptibility testing are advised whenever possible to manage and monitor mucormycosis.

SUBMITTER: Carvalhaes CG

PROVIDER: S-EPMC9960003 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific.

Carvalhaes Cecilia G CG Rhomberg Paul R PR Huband Michael D MD Pfaller Michael A MA Castanheira Mariana M

Journal of fungi (Basel, Switzerland) 20230211 2

Isavuconazole is the only US FDA-approved antifungal for treating invasive mucormycosis. We evaluated isavuconazole activity against a global collection of Mucorales isolates. Fifty-two isolates were collected during 2017-2020 from hospitals located in the USA, Europe, and the Asia-Pacific. Isolates were identified by MALDI-TOF MS and/or DNA sequencing and susceptibility tested by the broth microdilution method following CLSI guidelines. Isavuconazole (MIC<sub>50/90</sub>, 2/>8 mg/L) inhibited 5 ...[more]

PMID: 36836355

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Project description:The in vitro activity of isavuconazole against Mucorales isolates measured by EUCAST E.Def 9.2 and CLSI M38-A2 methodologies was investigated in comparison with those of amphotericin B, posaconazole, and voriconazole. Seventy-two isolates were included: 12 of Lichtheimia corymbifera, 5 of Lichtheimia ramosa, 5 of group I and 9 of group II of Mucor circinelloides, 9 of Rhizomucor pusillus, 26 of Rhizopus microsporus, and 6 of Rhizopus oryzae. Species identification was confirmed by internal transcribed spacer (ITS) sequencing. EUCAST MICs were read on day 1 (EUCAST-d1) and day 2 (EUCAST-d2), and CLSI MICs were read on day 2 (CLSI-d2). Isavuconazole MIC50s (range) (mg/liter) by EUCAST-d1, CLSI-d2, and EUCAST-d2 were 1 (0.125 to 16), 1 (0.125 to 2), and 4 (0.5 to >16), respectively, across all isolates. The similar values for comparator drugs were as follows: posaconazole, 0.25 (≤ 0.03 to >16), 0.25 (0.06 to >16), and 1 (0.06 to >16); amphotericin, 0.06 (≤ 0.03 to 0.5), 0.06 (≤ 0.03 to 0.25), and 0.125 (≤ 0.03 to 1); voriconazole, 16 (2 to >16), 8 (1 to >16), and >16 (8 to >16), respectively. Isavuconazole activity varied by species: Lichtheimia corymbifera, 1 (0.5 to 2), 1 (1 to 2), and 2 (1 to 4); Lichtheimia ramosa, 0.25 (0.125 to 0.5), 1 (0.5 to 2), and 2 (0.5 to 4); Rhizomucor pusillus, 0.5 (0.5 to 1), 1 (0.125 to 1), and 2 (1 to 2); Rhizopus microsporus, 1 (0.5 to 4), 0.5 (0.125 to 1), and 4 (1 to 8); and Rhizopus oryzae, 1 (0.5 to 4), 1 (0.125 to 2), and 4 (0.5 to 8), respectively, were more susceptible than Mucor circinelloides: group I, 8 (4 to 8), 4 (2 to 4), and 16 (2 to 16), respectively, and group II, 8 (1 to 16), 8 (1 to 8), and 16 (4 to >16), respectively. This was also observed for posaconazole. The essential agreement was best between EUCAST-d1 and CLSI-d2 (75% to 83%). Isavuconazole displayed in vitro activity against Mucorales isolates with the exception of Mucor circinelloides. The MICs were in general 1 to 3 steps higher than those for posaconazole. However, in the clinical setting this may be compensated for by the higher exposure at standard dosing.

Project description:We evaluated the activity of rezafungin and comparators, using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, against a worldwide collection of 2,205 invasive fungal isolates recovered from 2016 to 2018. Candida (n = 1,904 isolates; 6 species), Cryptococcus neoformans (n = 73), Aspergillus fumigatus (n = 183), and Aspergillus flavus (n = 45) isolates were tested for their susceptibility (S) to rezafungin as well as the comparators caspofungin, anidulafungin, micafungin, and azoles. Interpretive criteria were applied following CLSI published clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs). Isolates displaying non-wild-type (non-WT) echinocandin MIC values were sequenced for hot spot (HS) mutations. Rezafungin inhibited 99.8% of Candida albicans isolates (MIC50/90, 0.03/0.06 μg/ml), 95.7% of Candida glabrata isolates (MIC50/90, 0.06/0.12 μg/ml), 97.4% of Candida tropicalis isolates (MIC50/90, 0.03/0.06 μg/ml), 100.0% of Candida krusei isolates (MIC50/90, 0.03/0.06 μg/ml), and 100.0% of Candida dubliniensis isolates (MIC50/90, 0.06/0.12 μg/ml) at ≤0.12 μg/ml. All (329/329 [100.0%]) Candida parapsilosis isolates (MIC50/90,1/2 μg/ml) were inhibited by rezafungin at ≤4 μg/ml. Fluconazole resistance was detected among 8.6% of C. glabrata isolates, 12.5% of C. parapsilosis isolates, 3.2% of C. dubliniensis isolates, and 2.6% of C. tropicalis isolates. The activity of rezafungin against these 6 Candida spp. was similar to the activity of the other echinocandins. Detection of the HS mutation was performed by sequencing echinocandin-resistant or non-WT Candida isolates. Good activity against C. neoformans was observed for fluconazole and the other azoles, whereas the echinocandins, including rezafungin, displayed limited activity. Rezafungin displayed activity similar to that of the other echinocandins against A. fumigatus and A. flavus These in vitro data contribute to accumulating research demonstrating the potential of rezafungin for preventing and treating invasive fungal infections.

Project description:Background and aimsTo improve upon the estimation of 10-year cardiovascular disease (CVD) event risk for individuals without prior CVD or diabetes mellitus in the Asia-Pacific region by systematic recalibration of the SCORE2 risk algorithm.MethodsThe sex-specific and competing risk-adjusted SCORE2 algorithms were systematically recalibrated to reflect CVD incidence observed in four Asia-Pacific risk regions, defined according to country-level World Health Organization age- and sex-standardized CVD mortality rates. Using the same approach as applied for the original SCORE2 models, recalibration to each risk region was completed using expected CVD incidence and risk factor distributions from each region.ResultsRisk region-specific CVD incidence was estimated using CVD mortality and incidence data on 8 405 574 individuals (556 421 CVD events). For external validation, data from 9 560 266 individuals without previous CVD or diabetes were analysed in 13 prospective studies from 12 countries (350 550 incident CVD events). The pooled C-index of the SCORE2 Asia-Pacific algorithms in the external validation datasets was .710 [95% confidence interval (CI) .677-.744]. Cohort-specific C-indices ranged from .605 (95% CI .597-.613) to .840 (95% CI .771-.909). Estimated CVD risk varied several-fold across Asia-Pacific risk regions. For example, the estimated 10-year CVD risk for a 50-year-old non-smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and high-density lipoprotein cholesterol of 1.3 mmol/L, ranged from 7% for men in low-risk countries to 14% for men in very-high-risk countries, and from 3% for women in low-risk countries to 13% for women in very-high-risk countries.ConclusionsThe SCORE2 Asia-Pacific algorithms have been calibrated to estimate 10-year risk of CVD for apparently healthy people in Asia and Oceania, thereby enhancing the identification of individuals at higher risk of developing CVD across the Asia-Pacific region.

Dataset Information

Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific.

Publications

Antifungal Activity of Isavuconazole and Comparator Agents against Contemporaneous Mucorales Isolates from USA, Europe, and Asia-Pacific.

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