A comparative study of the in vitro susceptibilities of clinical and laboratory-selected resistant isolates of Aspergillus spp. to amphotericin B, itraconazole, voriconazole and posaconazole (SCH 56592)

Elias Kurian Manavathu, Jessica L. Cutright, David Loebenberg, Pranatharthi H. Chandrasekar

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

We investigated the in vitro susceptibilities of clinical and laboratory-selected Aspergillus spp. to posaconazole, and compared the results with those obtained for amphotericin B, itraconazole and voriconazole. Conidial suspensions from clinical isolates (284 Aspergillus fumigatus, 66 Aspergillus niger, 31 Aspergillus flavus and 43 Aspergillus spp.) and laboratory-selected resistant A. fumigatus isolates (15 resistant to amphotericin B, 25 to itraconazole and 12 to voriconazole) were prepared and their susceptibilities to various antifungal agents determined using a previously described broth macrodilution technique. The geometric mean MICs (mg/L) of posaconazole for A. fumigatus (0.17 ± 0.11) and non-A. fumigatus aspergilli (0.16 ± 0.28) were significantly lower (P ≤ 0.05) than those for amphotericin B, itraconazole and voriconazole. Amphotericin B-resistant A. fumigatus isolates were as susceptible to posaconazole as the parental strain. Itraconazole- and voriconazole-resistant isolates showed low-level (two- to three-fold increase in MICs) cross-resistance to posaconazole. The minimum fungicidal concentrations (mg/L) of posaconazole for A. fumigatus (n = 58) and non-A. fumigatus aspergilli (n = 40) were 4.45 ± 2.70 (range 0.25-8) and 4.14 ± 3.03 (range 0.5-8), respectively. Time-kill studies showed that the fungicidal activity of posaconazole against A. fumigatus is time- and concentration-dependent (for example, posaconazole 4 mg/L killed >99% of A. fumigatus conidia within 24 h). These results suggest that overall, posaconazole has better activity and a smaller range of MICs for Aspergillus spp., including those with reduced susceptibility to amphotericin B, itraconazole and voriconazole.

Original languageEnglish (US)
Pages (from-to)229-234
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume46
Issue number2
StatePublished - Sep 2 2000

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Aspergillus fumigatus
Itraconazole
Amphotericin B
Aspergillus
posaconazole
In Vitro Techniques
Voriconazole
Aspergillus flavus
Fungal Spores
Aspergillus niger
Antifungal Agents
Suspensions

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

A comparative study of the in vitro susceptibilities of clinical and laboratory-selected resistant isolates of Aspergillus spp. to amphotericin B, itraconazole, voriconazole and posaconazole (SCH 56592). / Manavathu, Elias Kurian; Cutright, Jessica L.; Loebenberg, David; Chandrasekar, Pranatharthi H.

In: Journal of Antimicrobial Chemotherapy, Vol. 46, No. 2, 02.09.2000, p. 229-234.

Research output: Contribution to journalArticle

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abstract = "We investigated the in vitro susceptibilities of clinical and laboratory-selected Aspergillus spp. to posaconazole, and compared the results with those obtained for amphotericin B, itraconazole and voriconazole. Conidial suspensions from clinical isolates (284 Aspergillus fumigatus, 66 Aspergillus niger, 31 Aspergillus flavus and 43 Aspergillus spp.) and laboratory-selected resistant A. fumigatus isolates (15 resistant to amphotericin B, 25 to itraconazole and 12 to voriconazole) were prepared and their susceptibilities to various antifungal agents determined using a previously described broth macrodilution technique. The geometric mean MICs (mg/L) of posaconazole for A. fumigatus (0.17 ± 0.11) and non-A. fumigatus aspergilli (0.16 ± 0.28) were significantly lower (P ≤ 0.05) than those for amphotericin B, itraconazole and voriconazole. Amphotericin B-resistant A. fumigatus isolates were as susceptible to posaconazole as the parental strain. Itraconazole- and voriconazole-resistant isolates showed low-level (two- to three-fold increase in MICs) cross-resistance to posaconazole. The minimum fungicidal concentrations (mg/L) of posaconazole for A. fumigatus (n = 58) and non-A. fumigatus aspergilli (n = 40) were 4.45 ± 2.70 (range 0.25-8) and 4.14 ± 3.03 (range 0.5-8), respectively. Time-kill studies showed that the fungicidal activity of posaconazole against A. fumigatus is time- and concentration-dependent (for example, posaconazole 4 mg/L killed >99{\%} of A. fumigatus conidia within 24 h). These results suggest that overall, posaconazole has better activity and a smaller range of MICs for Aspergillus spp., including those with reduced susceptibility to amphotericin B, itraconazole and voriconazole.",
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