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The Annals of Pharmacotherapy: Vol. 37, No. 4, pp. 595. DOI 10.1345/aph.1C114a
© 2003 Harvey Whitney Books Company.
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Comment: caspofungin acetate for treatment of invasive fungal infections

Jeff Chan, BSc Pharm

Pharmacy Manager Department of Pharmacy Thunder Bay Regional Hospital 325 South Archibald Street Thunder Bay, Ontario P7E 1G6 Canada FAX 807/623-8459 E-mail chanj{at}tbh.net

Published Online, February 20, 2003. www.theannals.com, DOI 10.1345/aph.1C114a

TO THE EDITOR: The authors provide a good overview of caspofungin; however, a developing area was not discussed.1 The use of combination therapy has been established to reduce the potential for the development of resistance or to increase the effectiveness of the therapy. There have been a number of studies reporting that caspofungin combination therapy might be more effective than single-agent therapy against various organisms.2-5

In a study investigating the in vitro susceptibility of Aspergillus fumigatus to paired combinations of a number of antifungal agents, the combination of caspofungin and amphotericin B was synergistic, while caspofungin and voriconazole were additive.2 Results were evaluated by radiometric assay and fractional inhibitory concentration index (FIC). The authors concluded that 2-drug combinations of an echinocandin with a polyene or azole may be more effective against A. fumigatus than using them individually.

In another study, Perea et al.3 investigated the interaction between caspofungin and voriconazole in vitro using Aspergillus spp. isolates obtained from patients. Synergy, defined as an FIC <=1 or additive effect (defined as FIC 1.0) was observed in 87.5% and 4.2% of the interactions, respectively.

Recently, Kirkpatrick et al.4 investigated the antifungal activity of caspofungin alone or in combination with voriconazole in a neutropenic guinea pig model with invasive aspergillosis. The authors reported that the combination of caspofungin and voriconazole was as effective as voriconazole alone in reducing mortality; however, the combination was more effective in reducing colony counts and sterilizing tissue cultures.

Finally, Arikan et al.5 investigated the in vitro interaction of caspofungin and amphotericin B against clinical isolates of Aspergillus spp. and Fusarium spp. They reported that the combination was synergistic or additive for more than half of the isolates of both bacteria. Of interest was the synergistic or additive effect of caspofungin against Fusarium spp., despite having no activity against this fungus.

While studies are needed to determine the clinical relevance of these results, certainly the possibility of combination therapy is an exciting prospect for these difficult-to-treat infections.

References

  1. Pacetti SA, Gelone SP. Caspofungin acetate for treatment of invasive fungal infections. Ann Pharmacother 2003;37:90-8.[Abstract/Free Full Text]
  2. Manavathu EK, Ganesan LT, Cutright JL, Chandrasekar PA. In vitro antifungal activity of voriconazole in two-drug combination with micafungin, caspofungin, and amphotericin B (abstract J-125). Presented at: 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago: September 22–25, 2001.
  3. Perea S, Gonzalez G, Fothergill AW, Kirkpatrick WR, Rinaldi MG, Patterson TF. In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. Antimicrob Agents Chemother 2002;46:3039-41.[Abstract/Free Full Text]
  4. Kirkpatrick WR, Perea S, Coco BJ, Patterson TF. Efficacy of caspofungin alone and in combination with voriconazole in a guinea pig model of invasive aspergillosis. Antimicrob Agents Chemother 2002;46:2564-8.[Abstract/Free Full Text]
  5. Arikan S, Lozano-Chio M, Paetznick V, Rex JH. In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp. Antimicrob Agents Chemother 2002;46:245-7.[Abstract/Free Full Text]



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Comment: caspofungin acetate for treatment of invasive fungal infections
Ann. Pharmacother., December 1, 2003; 37(12): 1919 - 1919.
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