Skip to main content

Advertisement

SpringerLink
Log in

The efficacy of voriconazole in 24 ocular Fusarium infections

  • Clinical and Epidemiological Study
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

We examined, retrospectively, the efficacy of voriconazole in Fusarium eye infections.

Methods

Voriconazole-treated patients with proven or probable keratitis or endophthalmitis from the voriconazole database (9 patients) and six French ophthalmology departments (15 patients) were included. Sociodemographic features, predisposing factors, history of corneal trauma, associated ocular conditions, other diseases and prior therapies were analysed. Investigator-determined success was defined as infection resolution with medical treatment. Failure was no response or persistent infection and required surgery.

Results

Most patients were Caucasian (83 %) and male (71 %). The infection was keratitis (63 %) or endophthalmitis (37 %) and proven in 23 (96 %). Prior therapy included topical and/or systemic amphotericin (46 %), fluconazole (17 %) or others (33 %), often in combination. Causative fungi were Fusarium solani (14, 58 %), Fusarium moniliforme (1), Fusarium oxysporum (1) and Fusarium spp. (8). Voriconazole was administered systemically, topically and/or by intraocular injection, and 16 patients (67 %) received salvage and eight primary therapy. The overall response was 67 % (73 % keratitis and 56 % endophthalmitis) but seven patients required adjunctive surgery. However, response was 63 % for eight primary therapy patients and 69 % for 16 salvage therapy patients. Response by species was Fusarium solani 64 % (9/14) and all others 80 % (8/10). In 13 patients (77 %), voriconazole was used in combination (response 69 vs. 64 % alone) with topical [amphotericin B 10/24 (42 %), caspofungin 5 (21 %), natamycin 1 (4 %)] and systemic agents [caspofungin 3 (13 %), amphotericin 2 (8 %)].

Conclusions

Topical and systemic voriconazole appears to be effective alone or in combination with other agents for treating severe Fusarium keratitis or endophthalmitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Xie L, Zhong W, Shi W, Sun S. Spectrum of fungal keratitis in north China. Ophthalmology. 2006;113:1943–8.

    Article  PubMed  Google Scholar 

  2. Chang DC, Grant GB, O’Donnell K, et al. Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA. 2006;296:953–63.

    Article  PubMed  CAS  Google Scholar 

  3. Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007;20:695–704.

    Article  PubMed  CAS  Google Scholar 

  4. Tuft SJ, Tullo AB. Fungal keratitis in the United Kingdom 2003–2005. Eye. 2009;23:1308–13.

    Article  PubMed  CAS  Google Scholar 

  5. Rondeau N, Bourcier T, Chaumeil C, et al. Fungal keratitis at the Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts: retrospective study of 19 cases. J Fr Ophtalmol. 2002;25:890–6.

    PubMed  CAS  Google Scholar 

  6. Senthilkumari S, Lalitha P, Prajna NV, et al. Single and multidose ocular kinetics and stability analysis of extemporaneous formulation of topical voriconazole in humans. Curr Eye Res. 2010;35:953–60.

    Article  PubMed  CAS  Google Scholar 

  7. Shen YC, Wang CY, Tsai HY, Lee HN. Intracameral voriconazole injection in the treatment of fungal endophthalmitis resulting from keratitis. Am J Ophthalmol. 2010;149:916–21.

    Article  PubMed  CAS  Google Scholar 

  8. Lau D, Leung L, Ferdinands M, et al. Penetration of 1 % voriconazole eye drops into human vitreous humour: a prospective, open-label study. Clin Exp Ophthalmol. 2009;37:197–200.

    Article  Google Scholar 

  9. Hariprasad SM, Mieler WF, Holz ER, et al. Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol. 2004;122:42–7.

    Article  PubMed  CAS  Google Scholar 

  10. Vemulakonda GA, Hariprasad SM, Mieler WF, Prince RA, Shah GK, Van Gelder RN. Aqueous and vitreous concentrations following topical administration of 1 % voriconazole in humans. Arch Ophthalmol. 2008;126:18–22.

    Article  PubMed  CAS  Google Scholar 

  11. Hariprasad SM, Mieler WF, Lin TK, Sponsel WE, Graybill JR. Voriconazole in the treatment of fungal eye infections: a review of current literature. Br J Ophthalmol. 2008;92:871–8.

    Article  PubMed  CAS  Google Scholar 

  12. Riddell J 4th, Comer GM, Kauffman CA. Treatment of endogenous fungal endophthalmitis: focus on new antifungal agents. Clin Infect Dis. 2011;52:648–53.

    Article  PubMed  CAS  Google Scholar 

  13. Prajna NV, Mascarenhas J, Krishnan T, et al. Comparison of natamycin and voriconazole for the treatment of fungal keratitis. Arch Ophthalmol. 2010;128:672–8.

    Article  PubMed  CAS  Google Scholar 

  14. Arora R, Gupta D, Goyal J, Kaur R. Voriconazole versus natamycin as primary treatment in fungal corneal ulcers. Clin Exp Ophthalmol. 2011;39:434–40.

    Article  Google Scholar 

  15. Tu EY. Alternaria keratitis: clinical presentation and resolution with topical fluconazole or intrastromal voriconazole and topical caspofungin. Cornea. 2009;28:116–9.

    Article  PubMed  Google Scholar 

  16. Bunya VY, Hammersmith KM, Rapuano CJ, Ayres BD, Cohen EJ. Topical and oral voriconazole in the treatment of fungal keratitis. Am J Ophthalmol. 2007;143:151–3.

    Article  PubMed  CAS  Google Scholar 

  17. Klont RR, Eggink CA, Rijs AJ, Wesseling P, Verweij PE. Successful treatment of Fusarium keratitis with cornea transplantation and topical and systemic voriconazole. Clin Infect Dis. 2005;40:e110–2.

    Article  PubMed  Google Scholar 

  18. Cakir M, Imamoğlu S, Cekiç O, et al. An outbreak of early-onset endophthalmitis caused by Fusarium species following cataract surgery. Curr Eye Res. 2009;34:988–95.

    Article  PubMed  CAS  Google Scholar 

  19. Durand ML, Kim IK, D’Amico DJ, et al. Successful treatment of Fusarium endophthalmitis with voriconazole and Aspergillus endophthalmitis with voriconazole plus caspofungin. Am J Ophthalmol. 2005;140:552–4.

    Article  PubMed  CAS  Google Scholar 

  20. Reis A, Sundmacher R, Tintelnot K, Agostini H, Jensen HE, Althaus C. Successful treatment of ocular invasive mould infection (fusariosis) with the new antifungal agent voriconazole. Br J Ophthalmol. 2000;84:932–3.

    Article  PubMed  CAS  Google Scholar 

  21. Bang S, Edell E, Eghrari AO, Gottsch JD. Treatment with voriconazole in 3 eyes with resistant Acanthamoeba keratitis. Am J Ophthalmol. 2010;149:66–9.

    Article  PubMed  CAS  Google Scholar 

  22. Schuster FL, Guglielmo BJ, Visvesvara GS. In-vitro activity of miltefosine and voriconazole on clinical isolates of free-living amebas: Balamuthia mandrillaris, Acanthamoeba spp., and Naegleria fowleri. J Eukaryot Microbiol. 2006;53:121–6.

    Article  PubMed  CAS  Google Scholar 

  23. Tu EY, Joslin CE, Shoff ME. Successful treatment of chronic stromal Acanthamoeba keratitis with oral voriconazole monotherapy. Cornea. 2010;29:1066–8.

    Article  PubMed  Google Scholar 

  24. Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol. 2006;46:235–43.

    Article  PubMed  CAS  Google Scholar 

  25. Kadikoy H, Barkmeier A, Peck B, Carvounis PE. Persistent photopsia following course of oral voriconazole. J Ocul Pharmacol Ther. 2010;26:387–8.

    Article  PubMed  CAS  Google Scholar 

  26. Al-Badriyeh D, Neoh CF, Stewart K, Kong DC. Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis. Clin Ophthalmol. 2010;4:391–405.

    PubMed  Google Scholar 

  27. Bullock JD. An outbreak of Fusarium keratitis associated with contact lens use in the northeastern United States. Cornea. 2008;27:973–4.

    Article  PubMed  Google Scholar 

  28. Gaujoux T, Borsali E, Goldschmidt P, et al. Fungal keratitis in France. Acta Ophthalmol. 2011;89:e215–6.

    Article  PubMed  Google Scholar 

  29. Rao SK, Lam PT, Li EY, Yuen HK, Lam DS. A case series of contact lens-associated Fusarium keratitis in Hong Kong. Cornea. 2007;26:1205–9.

    Article  PubMed  Google Scholar 

  30. Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003;36:1122–31.

    Article  PubMed  CAS  Google Scholar 

  31. Lortholary O, Obenga G, Biswas P, et al. International retrospective analysis of 73 cases of invasive fusariosis treated with voriconazole. Antimicrob Agents Chemother. 2010;54:4446–50.

    Article  PubMed  CAS  Google Scholar 

  32. Stanzani M, Tumietto F, Vianelli N, Baccarani M. Update on the treatment of disseminated fusariosis: focus on voriconazole. Ther Clin Risk Manag. 2007;3:1165–73.

    PubMed  CAS  Google Scholar 

  33. Dupuis A, Tournier N, Le Moal G, Venisse N. Preparation and stability of voriconazole eye drop solution. Antimicrob Agents Chemother. 2009;53:798–9.

    Article  PubMed  CAS  Google Scholar 

  34. Breit SM, Hariprasad SM, Mieler WF, Shah GK, Mills MD, Grand MG. Management of endogenous fungal endophthalmitis with voriconazole and caspofungin. Am J Ophthalmol. 2005;139:135–40.

    Article  PubMed  CAS  Google Scholar 

  35. Oude Lashof AML, Rothova A, Sobel JD, et al. Ocular manifestations of candidemia. Clin Infect Dis. 2011;53:262–8.

    Article  PubMed  Google Scholar 

  36. Kernt M, Kampik A. Intracameral voriconazole: in vitro safety for human ocular cells. Toxicology. 2009;258:84–93.

    Article  PubMed  CAS  Google Scholar 

  37. Kernt M, Neubauer AS, De Kaspar HM, Kampik A. Intravitreal voriconazole: in vitro safety-profile for fungal endophthalmitis. Retina. 2009;29:362–70.

    Article  PubMed  Google Scholar 

  38. Lau D, Fedinands M, Leung L, et al. Penetration of voriconazole, 1 %, eyedrops into human aqueous humor: a prospective open-label study. Arch Ophthalmol. 2008;126:343–6.

    Article  PubMed  CAS  Google Scholar 

  39. Galarreta DJ, Tuft SJ, Ramsay A, Dart JK. Fungal keratitis in London: microbiological and clinical evaluation. Cornea. 2007;26:1082–6.

    Article  PubMed  Google Scholar 

  40. Espinel-Ingroff A, Johnson E, Hockey H, Troke P. Activities of voriconazole, itraconazole and amphotericin B in vitro against 590 moulds from 323 patients in the voriconazole Phase III clinical studies. J Antimicrob Chemother. 2008;61:616–20.

    Article  PubMed  CAS  Google Scholar 

  41. Azor M, Cano J, Gené J, Guarro J. High genetic diversity and poor in vitro response to antifungals of clinical strains of Fusarium oxysporum. J Antimicrob Chemother. 2009;63:1152–5.

    Article  PubMed  CAS  Google Scholar 

  42. Azor M, Gené J, Cano J, Guarro J. Universal in vitro antifungal resistance of genetic clades of the Fusarium solani species complex. Antimicrob Agents Chemother. 2007;51:1500–3.

    Article  PubMed  CAS  Google Scholar 

  43. Pfaller MA, Messer SA, Hollis RJ, Jones RN; SENTRY Participants Group. Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000. Antimicrob Agents Chemother. 2002;46:1032–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

P.T. received an honorarium from Pfizer in connection with the data finalisation, analysis and writing of this manuscript. G. O. was paid consultant to Pfizer for the collection of the French Mycosis Group data for this manuscript.

Conflict of interest

P. T. was previously an employee of and then a consultant to Pfizer; G.O. none to declare; T.G. none to declare; P.G. none to declare; A.-L.B. none to declare; M. C. none to declare; F. G. has received speaker fees from Schering and MSD; D. P. none to declare; S. R. none to declare; K. S. none to declare; V. B. none to declare; O. L. is a member of the speaker bureaus of Pfizer, MSD, Astellas and Gilead Sciences. Pfizer had no decision-making role in the design, execution, analysis or reporting of this research.

Author information

Authors and Affiliations

  1. The Old Court, 74a, Kingsgate Avenue, Broadstairs, Kingsgate, Kent, CT10 3LW, UK

    P. Troke

  2. Service des Maladies Infectieuses et Tropicales, Centre d’Infectiologie Necker Pasteur, Hôpital Necker Enfants Malades, Université Paris-Descartes, Paris, France

    G. Obenga & O. Lortholary

  3. Centre Hospitalier National d’Ophtalmologie des XV–XX, 28 rue de Charenton, 75012, Paris, France

    T. Gaujoux, P. Goldschmidt, C. Chaumeil & V. Borderie

  4. Faculté de Médecine, Université Lyon 1, Lyon, France

    A.-L. Bienvenu

  5. Hôtel Dieu, Paris, France

    M. Cornet

  6. Hôpital Jean Minjoz, Besançon, France

    F. Grenouillet

  7. Gabriel MontPied, Clermont-Ferrand, France

    D. Pons

  8. La Timone, Marseille, France

    S. Ranque

  9. Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques, Unité de Mycologie Moléculaire, Paris, France

    K. Sitbon & O. Lortholary

  10. CNRS URA3012, Paris, France

    O. Lortholary

Authors
  1. P. Troke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Obenga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Gaujoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Goldschmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A.-L. Bienvenu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Cornet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Grenouillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Pons
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. Ranque
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. Sitbon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C. Chaumeil
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. V. Borderie
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. O. Lortholary
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Troke.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Troke, P., Obenga, G., Gaujoux, T. et al. The efficacy of voriconazole in 24 ocular Fusarium infections. Infection 41, 15–20 (2013). https://doi.org/10.1007/s15010-012-0273-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-012-0273-2

Keywords

Search

Navigation