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Research Letters |

Successful Monitoring and Treatment of Intraocular Dissemination of Acanthamoeba FREE

Francisco Arnalich-Montiel, MD, PhD; Carmen M. Martín-Navarro, PhD; Jorge L. Alió, MD; Rogelio López-Vélez, MD, PhD; Enrique Martínez-Carretero, PhD; Basilio Valladares, PhD; José E. Piñero, PhD; Jacob Lorenzo-Morales, PhD
[+] Author Affiliations

Author Affiliations: Cornea Unit, Department of Ophthalmology (Drs Arnalich-Montiel and Alió) and Tropical Medicine and Clinical Parasitology Unit, Department of Infectious Diseases (Dr López-Vélez), Ramón y Cajal Hospital, Madrid, and University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Tenerife (Drs Martín-Navarro, Martínez-Carretero, Valladares, Piñero, and Lorenzo-Morales), Spain.


Arch Ophthalmol. 2012;130(11):1474-1475. doi:10.1001/archophthalmol.2012.2376.
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Intraocular spread of Acanthamoeba after keratitis is rare, being previously documented and microbiologically confirmed in 1 case of chorioretinitis1 and 1 case of endophthalmitis.2 Both occurred several months following penetrating keratoplasty (PK), were initially treated as suspected sterile inflammations, did not receive specific oral or intraocular treatment for Acanthamoeba, and finally required evisceration.

We report the first documented case, to our knowledge, of successful management of intraocular Acanthamoeba dissemination. Intraocular and systemic treatment was monitored through microbiological testing and polymerase chain reaction analysis of serial aqueous taps.

A 56-year-old man with Acanthamoeba keratitis and keratoconus underwent tectonic PK to treat keratitis that was unresponsive to chlorhexidine gluconate and eventually resulted in corneal perforation. Treatment after PK included topical chlorhexidine, moxifloxacin, cyclopentolate hydrochloride, and dexamethasone sodium phosphate as well as oral prednisolone (60 mg once daily) and tacrolimus (1 mg twice daily).

Five days after surgery, the patient reported blurred vision. The graft showed inferior edema, Descemet folds, mutton-fat keratic precipitates, and 4+ cells in the anterior chamber (AC) with a hypopyon (Figure 1A). Taps of the AC were taken and intravitreal vancomycin hydrochloride and ceftazidime were administered. Also, 100 μL of 1-μg/μL voriconazole solution was injected in the vitreous and AC owing to suspected Acanthamoeba dissemination. The AC tap result was positive for T4 Acanthamoeba by culture and polymerase chain reaction.3 Direct microscopical examination of an aliquot of the aqueous sample previously homogenized by gentle inversion showed 104 trophozoites/mL using a Coulter Z automatic cell counter and 90% viability as assessed using trypan blue dye exclusion.3 The voriconazole sensitivity test showed mean (SD) 90% inhibitory concentrations3 of 10.63 (0.46) μg/mL for cysts and 11.28 (0.32) μg/mL for trophozoites. Oral immunosuppression was stopped and treatment with topical voriconazole, 1%, oral voriconazole (200 mg twice daily), and trimethoprim/sulfamethoxazole (800/160 mg twice daily) was started.

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Figure 1. Anterior segment photograph of the patient's right eye 5 days after the therapeutic penetrating keratoplasty shows perikeratic hyperemia, corneal edema with Descemet folds, and mutton-fat keratic precipitates (A), and slitlamp examination after clinical resolution shows early signs of graft failure and pigmented keratic precipitates (B).

The clinical picture worsened during the next 3 days, then improved until clinical resolution 1 month after onset. Ocular echography ruled out vitreous involvement during follow-up. Second and third AC taps followed by voriconazole intraocular injection were performed at days 4 and 11 following the first tap; both were cultured and were positive for Acanthamoeba by polymerase chain reaction. A fourth tap without voriconazole injection confirmed microbiological cure at day 31 on culture and polymerase chain reaction analysis. Figure 2 shows the AC total and viable Acanthamoeba concentrations during follow-up.

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Figure 2. Evolution of total and viable Acanthamoeba concentrations in an aliquot of anterior chamber during follow-up until resolution.

The patient's maintenance regimen has been topical chlorhexidine, 0.02%, and voriconazole, 1%, 4 times daily with 200 mg of oral voriconazole twice daily for the last 6 months, without recurrence (Figure 1B). The corneal graft shows early signs of failure, and Descemet-stripping automated endothelial keratoplasty plus phacoemulsification is planned once clinical remission reaches 12 months.

We report the first case, to our knowledge, of a successful outcome in a patient with microbiological evidence of intraocular dissemination of Acanthamoeba. We believe success was based on 3 points that were not emphasized in previously reported cases: (1) early diagnosis; (2) successful combination of topical, oral, and intraocular therapy with drugs that can reach therapeutic levels in aqueous and vitreous4,5 and are effective in vivo6 for other Acanthamoeba infections; and (3) guiding treatment by effective monitoring of the response by Acanthamoeba.

We think oral and topical administration of voriconazole must have achieved a sustained therapeutic dose and frequent administration of intraocular voriconazole produced high peak levels, increasing effectiveness. Topical chlorhexidine was used before the PK but the keratitis worsened, raising the question of its effectiveness in our patient. It is unknown whether topical chlorhexidine can reach aqueous therapeutic levels; however, rabbit studies have shown that frequent instillation of chlorhexidine, 0.02%, in epithelialized corneas7 produces concentrations 10 to 40 times lower than voriconazole but, in our experience, a similar 90% inhibitory concentration. Moreover, in the other described cases, topical antiseptics such as chlorhexidine used after PK did not prevent endophthalmitis. Therefore, we believe chlorhexidine did not play a major role in our case. The susceptibility of Acanthamoeba to trimethoprim/sulfamethoxazole, also used in our patient, is based on a few reports8; we have not tested the susceptibility of the patient's strain and cannot be sure of its real contribution.

Correspondence: Dr Arnalich-Montiel, Servicio de Oftalmología, Hospital Ramón y Cajal de Madrid, Carretera de Colmenar Viejo km 9.100, 28034 Madrid, Spain (farnalich@gmail.com).

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported in part by project RICET (project RD06/0021/0005 of the Programme of Redes Temáticas de Investigación Cooperativa, Fondo de Investigación Sanitaria), Spanish Ministry of Health, and the project “Protozoosis emergentes por amebas de vida libre: aislamiento y caracterizacion molecular, identificacion de cepas transportadas de otros agentes patogenos y busqueda de quimioterapias” PO10/01298, Spanish Ministry of Science and Innovation. This work was also supported by grants to Dr Arnalich-Montiel from DGTATX, Ministerio de Sanidad y Consumo (Proyecto TRA-036), and Fundación Mutua Madrileña. Dr Lorenzo-Morales was supported by the Ramón y Cajal subprogram RYC-2011-08863 of the Spanish Ministry of Science and Innovation.

Moshari A, McLean IW, Dodds MT, Damiano RE, McEvoy PL. Chorioretinitis after keratitis caused by Acanthamoeba: case report and review of the literature.  Ophthalmology. 2001;108(12):2232-2236
PubMed   |  Link to Article
Davis MJ, Packo KH, Epstein RJ, Grostern RJ, Cohen JA. Acanthamoeba endophthalmitis following penetrating keratoplasty for Acanthamoeba keratitis.  Arch Ophthalmol. 2010;128(4):505-506
PubMed   |  Link to Article
Martín-Navarro CM, Lorenzo-Morales J, Cabrera-Serra MG,  et al.  The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife, Canary Islands, Spain.  J Med Microbiol. 2008;57(pt 11):1399-1404
PubMed   |  Link to Article
Shen YC, Wang MY, Wang CY,  et al.  Pharmacokinetics of intracameral voriconazole injection.  Antimicrob Agents Chemother. 2009;53(5):2156-2157
PubMed   |  Link to Article
Hariprasad SM, Mieler WF, Holz ER,  et al.  Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans.  Arch Ophthalmol. 2004;122(1):42-47
PubMed   |  Link to Article
Tu EY, Joslin CE, Shoff ME. Successful treatment of chronic stromal acanthamoeba keratitis with oral voriconazole monotherapy.  Cornea. 2010;29(9):1066-1068
PubMed   |  Link to Article
Banich AM, Bu P, Jacob G,  et al.  Penetration of chlorhexidine into the rabbit anterior chamber following topical administration.  Invest Ophthalmol Vis Sci. 2003;44:E-abstract 3769http://abstracts.iovs.org/cgi/content/abstract/44/5/3769. Accessed May 15, 2012
Singhal T, Bajpai A, Kalra V,  et al.  Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials.  Pediatr Infect Dis J. 2001;20(6):623-627
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Anterior segment photograph of the patient's right eye 5 days after the therapeutic penetrating keratoplasty shows perikeratic hyperemia, corneal edema with Descemet folds, and mutton-fat keratic precipitates (A), and slitlamp examination after clinical resolution shows early signs of graft failure and pigmented keratic precipitates (B).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Evolution of total and viable Acanthamoeba concentrations in an aliquot of anterior chamber during follow-up until resolution.

Tables

References

Moshari A, McLean IW, Dodds MT, Damiano RE, McEvoy PL. Chorioretinitis after keratitis caused by Acanthamoeba: case report and review of the literature.  Ophthalmology. 2001;108(12):2232-2236
PubMed   |  Link to Article
Davis MJ, Packo KH, Epstein RJ, Grostern RJ, Cohen JA. Acanthamoeba endophthalmitis following penetrating keratoplasty for Acanthamoeba keratitis.  Arch Ophthalmol. 2010;128(4):505-506
PubMed   |  Link to Article
Martín-Navarro CM, Lorenzo-Morales J, Cabrera-Serra MG,  et al.  The potential pathogenicity of chlorhexidine-sensitive Acanthamoeba strains isolated from contact lens cases from asymptomatic individuals in Tenerife, Canary Islands, Spain.  J Med Microbiol. 2008;57(pt 11):1399-1404
PubMed   |  Link to Article
Shen YC, Wang MY, Wang CY,  et al.  Pharmacokinetics of intracameral voriconazole injection.  Antimicrob Agents Chemother. 2009;53(5):2156-2157
PubMed   |  Link to Article
Hariprasad SM, Mieler WF, Holz ER,  et al.  Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans.  Arch Ophthalmol. 2004;122(1):42-47
PubMed   |  Link to Article
Tu EY, Joslin CE, Shoff ME. Successful treatment of chronic stromal acanthamoeba keratitis with oral voriconazole monotherapy.  Cornea. 2010;29(9):1066-1068
PubMed   |  Link to Article
Banich AM, Bu P, Jacob G,  et al.  Penetration of chlorhexidine into the rabbit anterior chamber following topical administration.  Invest Ophthalmol Vis Sci. 2003;44:E-abstract 3769http://abstracts.iovs.org/cgi/content/abstract/44/5/3769. Accessed May 15, 2012
Singhal T, Bajpai A, Kalra V,  et al.  Successful treatment of Acanthamoeba meningitis with combination oral antimicrobials.  Pediatr Infect Dis J. 2001;20(6):623-627
PubMed   |  Link to Article

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