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In vitro synergy of natamycin and voriconazole against clinical isolates of Fusarium, Candida, Aspergillus and Curvularia spp
  1. Swatishree Sradhanjali1,
  2. Bandana Yein2,
  3. Savitri Sharma3,
  4. Sujata Das2
  1. 1 Ocular Microbiology Service, L V Prasad Eye Institute, Bhubaneswar, Odisha, India
  2. 2 Cornea Service, L V Prasad Eye Institute, Bhubaneswar, Odisha, India
  3. 3 Jhaveri Microbiology Centre, L V Prasad Eye Institute, Hyderabad, India
  1. Correspondence to Dr Sujata Das, Cornea Service, L V Prasad Eye Institute, Bhubaneswar, Odisha 751024, India; sujatadas{at}


Aim To determine the minimum inhibitory concentrations (MICs) of voriconazole and natamycin, alone and in combination, against the clinical isolates of Fungus and to evaluate the synergy between the drugs in an experimental in vitro study.

Methods In an experimental in vitro study, clinical isolates of Fusarium, Aspergillus, Candida and Curvularia spp were maintained on Sabouraud Dextrose Agar and used for the study. The MICs of natamycin and voriconazole, used alone and in combination, were evaluated by checkerboard microdilution technique based on the standard protocol proposed by the Clinical Laboratory Standards Institute. The interactions were assessed using the fractional inhibitory concentration (FIC) Index model.

Results Tested with all the clinical isolates, the MICs ranged between 0.125 and 8 µg/mL both for natamycin and voriconazole. In descending order, maximum synergism (FIC ≤0.5) was observed in Candida spp (33.3%) followed by Curvularia spp and Fusarium spp (23.1%). Synergism was least for Aspergillus spp (22.2%). However, at 61.5% (8/13), maximum additive effect (>0.5–1) was observed in Aspergillus spp and minimum (33.3%, 2/6) in Candida spp. Indifference (FIC value >1 and≤4) was observed in 22.2% (2/9) of Aspergillus spp, 15.4% (2/13) of Fusarium spp, 33.3% (2/6) of Candida spp and 23.1% (3/13) of Curvularia spp. No cases of antagonism (FIC >4) were observed.

Conclusions Natamycin and voriconazole in combination demonstrated more effective antifungal activity than single-use in vitro treatment in all species tested, which implies that these combinations may be helpful in treating fungal keratitis. There was no antagonism between these two drugs.

  • cornea
  • experimental laboratory
  • infection
  • microbiology

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  • Contributors All the authors included in this paper fulfil the criteria of authorship.

  • Competing interests None declared.

  • Ethics approval Institutional Review Board of the Institute (LEC07-13-070).

  • Provenance and peer review Not commissioned; externally peer reviewed.