Combined Treatment of Acanthamoeba Keratitis With Propamidine, Neomycin, and Polyhexamethylene Biguanide

Varga, John H.; Wolf, Thomas C.; Jensen, Harold G.; Parmley, Vernon C.; Rowsey, J. James

doi:10.1016/s0002-9394(14)74448-4

Cited by 64 publications

(26 citation statements)

References 13 publications

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“…Pentamidine, one of the aromatic diamidine compounds, has been found that it functioned against Pneumocystis carinii, the pathogen responsible for opportunistic infection which occurs in the majority of patients with AIDS (12,(18)(19)(20). Propamidine, another compound belonging to aromatic diamidines, is an antimicrobial agent used for the treatment of Acanthamoeba keratitis and other corneal infections (21,22). Recently, Chen et al found that the propamidine was also effictive against Botrytis cinerea (23).…”

Section: Discussionmentioning

confidence: 99%

Propamidine decreas mitochondrial complex III activity of Botrytis cinerea

Wu¹,

Jin²,

Feng³

et al. 2010

BMB Reports

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Propamidine, an aromatic diamidine compound, is widely used as an antimicrobial agent. To uncover its mechanism on pathogenetic fungi, Botrytis cinerea as an object was used to investigate effects of propamidine in this paper. The transmission electron microscope results showed that the mitochondrial membranes were collapsed after propamidine treatment, followed that mitochondria were disrupted. Inhibition of whole-cell and mitochondrial respiration by propamidine suggested that Propamidine is most likely an inhibitor of electron transport within Botrytis cinerea mitochondria. Furthermore, the mitochondrial complex III activity were inhibited by propamidine. [BMB reports 2010; 43(9): 614-621]

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Section: Discussionmentioning

confidence: 99%

Propamidine decreas mitochondrial complex III activity of Botrytis cinerea

Wu¹,

Jin²,

Feng³

et al. 2010

BMB Reports

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“…Although not licensed for therapeutic use, it has been employed as a successful experimental treatment for AK by Larkin et al (250). A combination of chlorhexidine digluconate (a bisbiguanide) with PHMB (a polymeric biguanide) or with aromatic diamidines such as hexamidine, pentamidine, and propamidine isethionate or PHMB and hexamidine with debridement has been reported for the treatment of AK (124,161,171,175,195,196,250,260,323,365,405,447,454,482). PHMB alone does not appear to be associated with toxicity, but other compounds used in combination with PHMB may exert untoward effects (195).…”

Section: Amebic Keratitismentioning

confidence: 99%

Acanthamoebaspp. as Agents of Disease in Humans

2003

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Acanthamoeba spp. are free-living amebae that inhabit a variety of air, soil, and water environments. However, these amebae can also act as opportunistic as well as nonopportunistic pathogens. They are the causative agents of granulomatous amebic encephalitis and amebic keratitis and have been associated with cutaneous lesions and sinusitis. Immuno compromised individuals, including AIDS patients, are particularly susceptible to infections with Acanthamoeba. The immune defense mechanisms that operate against Acanthamoeba have not been well characterized, but it has been proposed that both innate and acquired immunity play a role. The ameba's life cycle includes an active feeding trophozoite stage and a dormant cyst stage. Trophozoites feed on bacteria, yeast, and algae. However, both trophozoites and cysts can retain viable bacteria and may serve as reservoirs for bacteria with human pathogenic potential. Diagnosis of infection includes direct microscopy of wet mounts of cerebrospinal fluid or stained smears of cerebrospinal fluid sediment, light or electron microscopy of tissues, in vitro cultivation of Acanthamoeba, and histological assessment of frozen or paraffin-embedded sections of brain or cutaneous lesion biopsy material. Immunocytochemistry, chemifluorescent dye staining, PCR, and analysis of DNA sequence variation also have been employed for laboratory diagnosis. Treatment of Acanthamoeba infections has met with mixed results. However, chlorhexidine gluconate, alone or in combination with propamidene isethionate, is effective in some patients. Furthermore, effective treatment is complicated since patients may present with underlying disease and Acanthamoeba infection may not be recognized. Since an increase in the number of cases of Acanthamoeba infections has occurred worldwide, these protozoa have become increasingly important as agents of human disease

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“…The responsible amoeba has been detected in the human cornea in two forms: as fragile trophozoites and as resistant dormant cysts. The medical treatment of this ocular infection remains very difficult because of the lack of antiamoebic drugs effective against cysts, which are responsible for frequent and serious recurrences.Since the first medical cure reported in 1985 (16), propamidine isethionate, an antimicrobial agent belonging to the diamidine family, has been the basic drug recommended for use in treatment, which includes the use of topical neomycin sulfate and various imidazoles (2,5,7,8,15). Unfortunately, propamidine is poorly cysticidal and the resistance of some Acanthamoeba strains has been reported (6, 10).…”

mentioning

confidence: 99%

“…Since the first medical cure reported in 1985 (16), propamidine isethionate, an antimicrobial agent belonging to the diamidine family, has been the basic drug recommended for use in treatment, which includes the use of topical neomycin sulfate and various imidazoles (2,5,7,8,15). Unfortunately, propamidine is poorly cysticidal and the resistance of some Acanthamoeba strains has been reported (6,10).…”

mentioning

confidence: 99%

Amoebicidal efficiencies of various diamidines against two strains of Acanthamoeba polyphaga

Perrine

Chenu

Georges

et al. 1995

Antimicrob Agents Chemother

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The first medical cure of Acanthamoeba keratitis was obtained by use of propamidine isethionate. Since then, it has been the basic drug recommended for use in treatment. Because some Acanthamoeba strains have been reported to be resistant to propamidine and propamidine was found to be only weakly cysticidal, superior homologs such as butamidine, pentamidine, hexamidine, heptamidine, octamidine, and nonamidine were tested for their amoebicidal effects on two Acanthamoeba strains isolated from patients with keratitis. Trophozoicidal and cysticidal efficiencies were found to be increased from propamidine to nonamidine; i.e., when the alkyl chain connecting the two benzene rings in their molecular structures was elongated, in comparison with propamidine, hexamidine and octamidine were the most amoebicidal molecules. As a result of these data, a kinetic study carried out on propamidine, hexamidine, and octamidine demonstrated that the amoebicidal effects resulted from two events: the diffusion of molecules through the plasma membrane or the double wall of trophozoites or cysts, respectively, and the lethal effects of molecules on amoebic protoplasm. The diffusion kinetics were increased when the alkyl chain was elongated, i.e., with an increase in the lipophilic properties of molecules. In contrast, the lethal effect kinetics were found to be unchanged by this elongation, indicating that they originated from the cationic surface-active properties induced by the protonated amidine groups attached to each benzene ring, which themselves remained unchanged from one molecule to the other. These results strongly advocate the immediate replacement of propamidine by hexamidine in the medical treatment of Acanthamoeba keratitis; in France, 0.1% hexamidine eyedrops are available (Desomedine). The results also advocate clinical investigations on the efficiency and toxicity of octamidine, which appears to be the most amoebicidal diamidine in vitro.Acanthamoeba keratitis is a serious and potentially devastating corneal infection generally seen in soft contact lens wearers. The responsible amoeba has been detected in the human cornea in two forms: as fragile trophozoites and as resistant dormant cysts. The medical treatment of this ocular infection remains very difficult because of the lack of antiamoebic drugs effective against cysts, which are responsible for frequent and serious recurrences.Since the first medical cure reported in 1985 (16), propamidine isethionate, an antimicrobial agent belonging to the diamidine family, has been the basic drug recommended for use in treatment, which includes the use of topical neomycin sulfate and various imidazoles (2,5,7,8,15). Unfortunately, propamidine is poorly cysticidal and the resistance of some Acanthamoeba strains has been reported (6, 10). In the present study, superior homologs of propamidine were tested for their amoebicidal effects both on trophozoites and cysts with the intent of finding whether some of them are more amoebicidal and, especially, cysticidal than propamidine. At...

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Combined Treatment of Acanthamoeba Keratitis With Propamidine, Neomycin, and Polyhexamethylene Biguanide

Cited by 64 publications

References 13 publications

Propamidine decreas mitochondrial complex III activity of Botrytis cinerea

Propamidine decreas mitochondrial complex III activity of Botrytis cinerea

Acanthamoebaspp. as Agents of Disease in Humans

Amoebicidal efficiencies of various diamidines against two strains of Acanthamoeba polyphaga

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