In vitro susceptibility of filamentous fungal isolates from a corneal ulcer clinical trial.
OBJECTIVE
To describe the minimum inhibitory concentration (MIC) of fungal isolates to natamycin and voriconazole, and to compare these MICs to previous ocular susceptibility studies.


METHODS
Experimental laboratory study using isolates from a randomized clinical trial.


METHODS
The Mycotic Ulcer Treatment Trial I was a randomized, double-masked, multicenter trial comparing topical natamycin and voriconazole for fungal keratitis treatment. Susceptibility testing to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute methods. The relationship between organism and MIC was assessed. A literature review was performed to compare results to previous ocular susceptibility studies.


RESULTS
Of the 323 patients enrolled in the trial, MICs were available for 221 (68%). Fusarium (n = 126) and Aspergillus species (n = 52) were the most commonly isolated organisms. MICs to natamycin and voriconazole were significantly different across all genera (P < .001). The MIC median (MIC50) and 90th percentile (MIC90) for natamycin were equal to or higher than voriconazole for all organisms except Curvularia species. Compared to other organisms, Fusarium species isolates had the highest MICs to voriconazole and Aspergillus flavus isolates had the highest MICs to natamycin. Our results were similar to previous reports except that the voriconazole MIC90 against Aspergillus species was 2-fold higher and the natamycin MIC90 against Aspergillus fumigatus was 4-fold higher in our study.


CONCLUSIONS
In this large susceptibility study, Fusarium isolates were least susceptible to voriconazole and A flavus isolates were least susceptible to natamycin when compared to other filamentous fungi. In the future, susceptibility testing may help guide therapy if performed in a timely manner.
Aravind Eye Care System, Madurai, India.
Prajna
P
Lalitha
F.I. Proctor Foundation, University of California San Francisco, San Francisco, California.
Catherine Q
CQ
Sun
Aravind Eye Care System, Madurai, India.
N Venkatesh
NV
Prajna
Aravind Eye Care System, Madurai, India.
Rajarathinam
R
Karpagam
Aravind Eye Care System, Madurai, India.
Manoharan
M
Geetha
F.I. Proctor Foundation, University of California San Francisco, San Francisco, California.
Kieran S
KS
O'Brien
F.I. Proctor Foundation, University of California San Francisco, San Francisco, California.
Vicky
V
Cevallos
F.I. Proctor Foundation, University of California San Francisco, San Francisco, California; Department of Ophthalmology, University of California San Francisco, San Francisco, California.
Stephen D
SD
McLeod
F.I. Proctor Foundation, University of California San Francisco, San Francisco, California; Department of Ophthalmology, University of California San Francisco, San Francisco, California.
Nisha R
NR
Acharya
F.I. Proctor Foundation, University of California San Francisco, San Francisco, California; Department of Ophthalmology, University of California San Francisco, San Francisco, California; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California. Electronic address: tom.lietman@ucsf.edu.
Thomas M
TM
Lietman
D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D003320:Corneal Ulcer / Q000188:drug therapy / Q000382:microbiology*; D004311:Double-Blind Method; D015821:Eye Infections, Fungal / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D005658:Fungi / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000382:microbiology*; D010866:Natamycin / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D010866:Natamycin; D065819:Voriconazole