In Vitro Comparison of the Cysticidal Activity of Povidone Iodine, Natamycin, and Chlorhexidine

Purpose: keratitis often is refractory to medical and surgical therapy, primarily because of the remarkable resilience of cysts. In this study, we directly compared the cysticidal activity and potency of several candidate medical therapies in vitro.

Design: Experimental study.

Participants: In vitro specimens obtained from 9 patients with keratitis seen at the Francis I. Proctor Foundation from 2008 through 2012.

Methods: The minimum cysticidal concentration (MCC) of povidone iodine, natamycin, and chlorhexidine was investigated using an established assay technique. The relative potency of each agent was estimated starting with concentrations commonly used in clinical practice and determining the number of two-fold dilutions required to reach the MCC. Statistical comparisons of relative potency were performed using bootstrap simulations and permutation tests.

Main Outcome Measures: Minimum cysticidal concentration and the number of two-fold dilutions required to reach the MCC.

Results: The MCC for chlorhexidine ranged from 3.1 to 25 μg/ml (median, 12.5 μg/ml; interquartile range [IQR], 6.25-12.5 μg/ml), the MCC for natamycin ranged from 390.6 to 3125 μg/ml (median, 390.6 μg/ml; IQR, 390.6-781.2 μg/ml), and the MCC for povidone iodine ranged from 0.3 to 78.1 μg/ml (median, 2.4 μg/ml; IQR, 0.6-9.8 μg/ml). Doses commonly used in clinical practice (povidone iodine 1%, natamycin 5%, and chlorhexidine 0.04%) were approximately 12, 7, and 5 two-fold dilutions higher than the drug's corresponding median MCC, respectively ( < 0.001, comparing 3 drugs). Povidone iodine 1% had the highest potency of the 3 medications tested, requiring more dilutions than natamycin 5% ( < 0.001) and chlorhexidine 0.04% ( < 0.001) to reach the MCC.

Conclusions: All 3 medications demonstrated in vitro cysticidal activity in each of the 9 isolates. The potency of 1% povidone iodine was greater than standard formulations of natamycin or chlorhexidine. Although its clinical efficacy is yet to be determined, povidone iodine may be considered as a potential adjuvant treatment in cases of recalcitrant keratitis.