Evidence map›Paper›PMID 36005544›Full record

ArticleMycoses2022

Epidemiological cut-off values for itraconazole and ravuconazole for Madurella mycetomatis, the most common causative agent of mycetoma.

Bertrand Nyuykonge, Emmanuel E Siddig, Najwa Adam Mhmoud, Borna A Nyaoke, Eduard E Zijlstra, Annelies Verbon, Sahar Bakhiet, Ahmed H Fahal, Wendy W J van de Sande

Open access · hybridAbstract read
In one paragraph

Article in Mycoses, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
7.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Mycetoma.PLoS neglected tropical diseases · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 4 countries.

Bertrand NyuykongeDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.ORCID https://orcid.org/0000-0002-1454-6149
Emmanuel E SiddigMycetoma Research Centre, University of Khartoum, Khartoum, Sudan.
Najwa Adam MhmoudMycetoma Research Centre, University of Khartoum, Khartoum, Sudan.
Borna A NyaokeDrugs for Neglected Diseases initiative (DNDi), Nairobi, Kenya.ORCID https://orcid.org/0000-0001-9563-7108
Eduard E ZijlstraDrugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
Annelies VerbonDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.
Sahar BakhietMycetoma Research Centre, University of Khartoum, Khartoum, Sudan.
Ahmed H FahalMycetoma Research Centre, University of Khartoum, Khartoum, Sudan.
Wendy W J van de SandeDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, the Netherlands.
University of Khartoum · SDErasmus MC · NLDrugs for Neglected Diseases Initiative · CH

Funding

Drugs for Neglected Diseases Initiative
6 · The paper itself

Abstract

backgroundEumycetoma is a neglected tropical disease. It is a chronic inflammatory subcutaneous infection characterised by painless swellings which produce grains. It is currently treated with a combination of itraconazole and surgery. In an ongoing clinical study, the efficacy of fosravuconazole, the prodrug of ravuconazole, is being investigated. For both itraconazole and ravuconazole, no clinical breakpoints or epidemiological cut-off values (ECV) to guide treatment are currently available.

objectiveTo determine tentative ECVs for itraconazole and ravuconazole in Madurella mycetomatis, the main causative agent of eumycetoma. MATERIALS AND

methodsMinimal inhibitory concentrations (MICs) for itraconazole and ravuconazole were determined in 131 genetically diverse clinical M. mycetomatis isolates with the modified CLSI M38 broth microdilution method. The MIC distributions were established and used to determine ECVs with the ECOFFinder software. CYP51A sequences were sequenced to determine whether mutations occurred in this azole target gene, and comparisons were made between the different CYP51A variants and the MIC distributions.

resultsThe MICs ranged from 0.008 to 1 mg/L for itraconazole and from 0.002 to 0.125 mg/L for ravuconazole. The M. mycetomatis ECV for itraconazole was 1 mg/L and for ravuconazole 0.064 mg/L. In the wild-type population, two CYP51A variants were found for M. mycetomatis, which differed in one amino acid at position 499 (S499G). The MIC distributions for itraconazole and ravuconazole were similar between the two variants. No mutations linked to decreased susceptibility were found.

conclusionThe proposed M. mycetomatis ECV for itraconazole is 1 mg/L and for ravuconazole 0.064 mg/L.

Indexed as

MadurellaMycetomaAntifungal AgentsHumansItraconazoleThiazolesTriazolesAntifungal AgentsER 30346ItraconazoleThiazolesTriazolesazolesCYP51Aepidemiological cut-off valueseumycetomaMadurella mycetomatismycetoma

Identifiers

PMID36005544
PMCPMC9804462
OpenAlexW4288685192

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.