Dataset Information

Comparative activity of posaconazole and systemic azole agents against clinical isolates of filamentous fungi from a global surveillance programme.

ABSTRACT:

Objectives

The activity of mould-active azoles was evaluated against 397 filamentous fungi causing invasive mould infections (IMI) worldwide. In addition, a tentative posaconazole epidemiological cut-off value (ECV) against Aspergillus fumigatus was investigated.

Methods

Isolates were susceptibility tested by the CLSI reference broth microdilution methods. Species identification was confirmed by MALDI-TOF and/or sequencing analysis.

Results

Aspergillus spp. (81.9%) remained the most common organism causing IMI worldwide; approximately two-thirds of Aspergillus spp. recovered were A. fumigatus. In general, more than 90% of 220 A. fumigatus isolates were wild type (WT) to all mould-active azoles, except itraconazole (84.5% WT). The voriconazole non-susceptible (NS) A. fumigatus rate was 7.7% overall and was higher in Europe (12.9%) than in the other regions (0%-5.8%). Posaconazole (MIC₅₀/MIC₉₀, 0.25/0.5 mg/L) showed similar or slightly higher activity than voriconazole (MIC₅₀/MIC₉₀, 0.5/0.5 mg/L) and isavuconazole (MIC₅₀/MIC₉₀, 0.5/1 mg/L) against A. fumigatus. The mould-active azoles displayed similar activity against non-fumigatus Aspergillus (WT rates >93%), but differences were observed among the main species/sections. Posaconazole, voriconazole, and isavuconazole inhibited at their respective ECVs 100%, 97.0%, and 100% of A. section Nigri; 100%, 100%, and 93.8% of A. section Terrei; and 97.3%, 100%, and 100% of A. section Flavi isolates. Posaconazole displayed potency greater than or equal to the other azoles against the Mucorales group and Scedosporium spp.

Conclusions

Posaconazole and other mould-active azoles showed good activity against Aspergillus spp. causing IMI, but clinicians should be aware of regional rates of voriconazole-NS A. fumigatus.

SUBMITTER: Carvalhaes CG

PROVIDER: S-EPMC8251335 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Comparative activity of posaconazole and systemic azole agents against clinical isolates of filamentous fungi from a global surveillance programme.

Carvalhaes Cecilia G CG Rhomberg Paul R PR Pfaller Michael M Castanheira Mariana M

JAC-antimicrobial resistance 20210626 2

<h4>Objectives</h4>The activity of mould-active azoles was evaluated against 397 filamentous fungi causing invasive mould infections (IMI) worldwide. In addition, a tentative posaconazole epidemiological cut-off value (ECV) against <i>Aspergillus fumigatus</i> was investigated.<h4>Methods</h4>Isolates were susceptibility tested by the CLSI reference broth microdilution methods. Species identification was confirmed by MALDI-TOF and/or sequencing analysis.<h4>Results</h4><i>Aspergillus</i> spp. (8 ...[more]

PMID: 34223145

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Project description:ObjectivesTaniborbactam is a boronate-based β-lactamase inhibitor in clinical development in combination with cefepime.MethodsCefepime-taniborbactam and comparator broth microdilution MICs were determined for patient isolates of Enterobacterales (n = 20 725) and Pseudomonas aeruginosa (n = 7919) collected in 59 countries from 2018 to 2022. Taniborbactam was tested at a fixed concentration of 4 mg/L. Isolates with cefepime-taniborbactam MICs ≥ 16 mg/L underwent WGS. β-Lactamase genes were identified in additional meropenem-resistant isolates by PCR/Sanger sequencing.ResultsTaniborbactam reduced the cefepime MIC90 value for all Enterobacterales from >16 to 0.25 mg/L (>64-fold). At ≤16 mg/L, cefepime-taniborbactam inhibited 99.5% of all Enterobacterales isolates; >95% of isolates with MDR and ceftolozane-tazobactam-resistant phenotypes; ≥ 89% of isolates with meropenem-resistant and difficult-to-treat-resistant (DTR) phenotypes; >80% of isolates with meropenem-vaborbactam-resistant and ceftazidime-avibactam-resistant phenotypes; 100% of KPC-positive, 99% of OXA-48-like-positive, 99% of ESBL-positive, 97% of acquired AmpC-positive, 95% of VIM-positive and 76% of NDM-positive isolates. Against P. aeruginosa, taniborbactam reduced the cefepime MIC90 value from 32 to 8 mg/L (4-fold). At ≤16 mg/L, cefepime-taniborbactam inhibited 96.5% of all P. aeruginosa isolates; 85% of meropenem-resistant phenotype isolates; 80% of isolates with MDR and meropenem-vaborbactam-resistant phenotypes; >70% of isolates with DTR, ceftazidime-avibactam-resistant and ceftolozane-tazobactam-resistant phenotypes; and 82% of VIM-positive isolates. Multiple potential mechanisms of resistance, including carriage of IMP, or alterations in PBP3 (ftsI), porins (decreased permeability) and efflux (up-regulation) were present in most isolates with cefepime-taniborbactam MICs ≥ 16 mg/L.ConclusionsCefepime-taniborbactam exhibited potent in vitro activity against Enterobacterales and P. aeruginosa, and inhibited most carbapenem-resistant isolates, including those carrying serine carbapenemases or NDM/VIM MBLs.

Dataset Information

Comparative activity of posaconazole and systemic azole agents against clinical isolates of filamentous fungi from a global surveillance programme.

Objectives

Methods

Results

Conclusions

Publications

Comparative activity of posaconazole and systemic azole agents against clinical isolates of filamentous fungi from a global surveillance programme.

Similar Datasets

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