Synergy Testing of Antiamoebic Agents for Acanthamoeba: Antagonistic Effect of Voriconazole

Maya Talbott, Vicky Cevallos, Michael Chen, Stephanie A. Chin, Prajna Lalitha, Gerami D. Seitzman, Thomas M. Lietman, Jeremy D. Keenan

Research output: Contribution to journalArticle

Abstract

PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 μg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%-78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%-50.3%) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.

Original languageEnglish (US)
Pages (from-to)1309-1313
Number of pages5
JournalCornea
Volume38
Issue number10
DOIs
StatePublished - Oct 1 2019

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Acanthamoeba
Chlorhexidine
Acanthamoeba Keratitis
Growth
Pharmaceutical Preparations
Confidence Intervals
Drug Combinations
Voriconazole
Drug Interactions
Cysts
propamidine

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Talbott, M., Cevallos, V., Chen, M., Chin, S. A., Lalitha, P., Seitzman, G. D., ... Keenan, J. D. (2019). Synergy Testing of Antiamoebic Agents for Acanthamoeba: Antagonistic Effect of Voriconazole. Cornea, 38(10), 1309-1313. https://doi.org/10.1097/ICO.0000000000002055
Talbott, Maya ; Cevallos, Vicky ; Chen, Michael ; Chin, Stephanie A. ; Lalitha, Prajna ; Seitzman, Gerami D. ; Lietman, Thomas M. ; Keenan, Jeremy D. / Synergy Testing of Antiamoebic Agents for Acanthamoeba : Antagonistic Effect of Voriconazole. In: Cornea. 2019 ; Vol. 38, No. 10. pp. 1309-1313.
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abstract = "PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 μg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1{\%}, 95{\%} confidence interval 35.7{\%}-78.6{\%}) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5{\%}, 95{\%} confidence interval 14.3{\%}-50.3{\%}) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.",
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Talbott, M, Cevallos, V, Chen, M, Chin, SA, Lalitha, P, Seitzman, GD, Lietman, TM & Keenan, JD 2019, 'Synergy Testing of Antiamoebic Agents for Acanthamoeba: Antagonistic Effect of Voriconazole', Cornea, vol. 38, no. 10, pp. 1309-1313. https://doi.org/10.1097/ICO.0000000000002055

Synergy Testing of Antiamoebic Agents for Acanthamoeba : Antagonistic Effect of Voriconazole. / Talbott, Maya; Cevallos, Vicky; Chen, Michael; Chin, Stephanie A.; Lalitha, Prajna; Seitzman, Gerami D.; Lietman, Thomas M.; Keenan, Jeremy D.

In: Cornea, Vol. 38, No. 10, 01.10.2019, p. 1309-1313.

Research output: Contribution to journalArticle

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T1 - Synergy Testing of Antiamoebic Agents for Acanthamoeba

T2 - Antagonistic Effect of Voriconazole

AU - Talbott, Maya

AU - Cevallos, Vicky

AU - Chen, Michael

AU - Chin, Stephanie A.

AU - Lalitha, Prajna

AU - Seitzman, Gerami D.

AU - Lietman, Thomas M.

AU - Keenan, Jeremy D.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 μg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%-78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%-50.3%) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.

AB - PURPOSE: To determine whether combinations of commonly used antiamoebic agents display synergy in their ability to kill Acanthamoeba cysts in vitro. METHODS: Synergy testing was performed with a microdilution checkerboard assay on 10 clinical Acanthamoeba keratitis isolates collected at the Proctor Foundation from 2008 to 2012. Each isolate was exposed to pairwise combinations of chlorhexidine, propamidine, and voriconazole. The minimum cysticidal concentration (MCC) for each drug pair was estimated for each isolate, and the summed fractional cysticidal concentration (ΣFCC) was calculated for each drug combination in the checkerboard, with synergy defined as a lack of growth at a ΣFCC ≤ 0.5 and antagonism as growth at a ΣFCC > 4. RESULTS: Chlorhexidine and propamidine were cysticidal, with median MCCs of 12.5 (range 1.5-50) and 11.7 (range 0.2-250), respectively. Voriconazole was not cysticidal, with a median MCC of >10,000 μg/mL. The combination of chlorhexidine and propamidine did not markedly change the cysticidal activity compared with either drug alone. By contrast, voriconazole antagonized the cysticidal activity of both chlorhexidine and propamidine, with Acanthamoeba growth observed at antagonistic ΣFCCs in 27 of 49 (55.1%, 95% confidence interval 35.7%-78.6%) checkerboard combinations of voriconazole and chlorhexidine and in 58 of 147 (39.5%, 95% confidence interval 14.3%-50.3%) combinations of voriconazole and propamidine. CONCLUSIONS: In an in vitro assay, voriconazole reduced the cysticidal activity of 2 commonly used antiamoebic drugs. Although the in vivo drug interactions could be different, these observations may be useful in cases of nonhealing Acanthamoeba keratitis being treated with combination therapies that include voriconazole.

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