Disease Information

General Information of the Disease (ID: DIS00042)

• Name: Histoplasmosis
• ICD: ICD-11: 1F2A

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Fluconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Lanosterol 14-alpha demethylase (ERG11) [1]

• Resistant Disease: Histoplasmosis [ICD-11: 1F2A.0]
• Molecule Alteration: Missense mutation; p.Y136F
• Resistant Drug: Fluconazole
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Cryptococcus neoformans strain; 5207
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method assay
• Mechanism Description: In summary, fluconazole treatment of disseminated histoplasmosis in patients with AIDS was associated with induction of resistance to fluconazole and, to a lesser extent, to voriconazole. And the changes in susceptibility were due to tagert alterations which a single amino acid substitution in CYP51p at Y136 appeared to be responsible for the reduction in susceptibility seen in the relapse isolate.

Voriconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Cytochrome P450 sterol 14 alpha-demethylase (CYP51) [1]

• Resistant Disease: Histoplasmosis [ICD-11: 1F2A.0]
• Molecule Alteration: Missense mutation; p.Y136F
• Resistant Drug: Voriconazole
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Histoplasma capsulatum strain; 5037
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: NCCLS method assay
• Mechanism Description: In summary, fluconazole treatment of disseminated histoplasmosis in patients with AIDS was associated with induction of resistance to fluconazole and, to a lesser extent, to voriconazole. And the changes in susceptibility were due to tagert alterations which a single amino acid substitution in CYP51p at Y136 appeared to be responsible for the reduction in susceptibility seen in the relapse isolate.

References

• Ref 1: Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who failed fluconazole. J Antimicrob Chemother. 2006 Jun;57(6):1235-9. doi: 10.1093/jac/dkl133. Epub 2006 Apr 20.