Synthetic nanoparticle-conjugated bisindoles and hydrazinyl arylthiazole as novel antiamoebic agents against brain-eating amoebae.

Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that can cause life-threatening infections involving the central nervous system. The high mortality rates of these infections demonstrate an urgent need for novel treatment options against the amoebae. Considering that indole and thiazole compounds possess wide range of antiparasitic properties, novel bisindole and thiazole derivatives were synthesized and evaluated against the amoebae. The antiamoebic properties of four synthetic compounds i.e., two new bisindoles (2-Bromo-4-(di (1H-indol-3-yl)methyl)phenol (denoted as A1) and 2-Bromo-4-(di (1H-indol-3-yl)methyl)-6-methoxyphenol (A2)) and two known thiazole (4-(3-Nitrophenyl)-2-(2-(pyridin-3-ylmethylene)hydrazinyl)thiazole (A3) and 4-(Biphenyl-4-yl)-2-(2-(1-(pyridin-4-yl)ethylidene)hydrazinyl)thiazole (A4)) were evaluated against B. mandrillaris and N. fowleri. The ability of silver nanoparticle (AgNPs) conjugation to enrich antiamoebic activities of the compounds was also investigated. The synthetic heterocyclic compounds demonstrated up to 53% and 69% antiamoebic activities against B. mandrillaris and N. fowleri respectively, while resulting in up to 57% and 68% amoebistatic activities, respectively. Antiamoebic activities of the compounds were enhanced by up to 71% and 51% against B. mandrillaris and N. fowleri respectively, after conjugation with AgNPs. These compounds exhibited potential antiamoebic effects against B. mandrillaris and N. fowleri and conjugation of synthetic heterocyclic compounds with AgNPs enhanced their activity against the amoebae.

Nanoparticles based therapeutic efficacy against Acanthamoeba: Updates and future prospect.

Acanthamoeba sp. is a free living amoeba that causes severe, painful and fatal infections, viz. Acanthamoeba keratitis and granulomatous amoebic encephalitis among humans. Antimicrobial chemotherapy used against Acanthamoeba is toxic to human cells and show side effects as well. Infections due to Acanthamoeba also pose challenges towards currently used antimicrobial treatment including resistance and transformation of trophozoites to resistant cyst forms that can lead to recurrence of infection. Therapeutic agents targeting central nervous system infections caused by Acanthamoeba should be able to cross blood-brain barrier. Nanoparticles based drug delivery put forth an effective therapeutic method to overcome the limitations of currently used antimicrobial chemotherapy. In recent years, various researchers investigated the effectiveness of nanoparticles conjugated drug and/or naturally occurring plant compounds against both trophozoites and cyst form of Acanthamoeba. In the current review, a reasonable effort has been made to provide a comprehensive overview of various nanoparticles tested for their efficacy against Acanthamoeba. This review summarizes the noteworthy details of research performed to elucidate the effect of nanoparticles conjugated drugs against Acanthamoeba.

Demodex-induced Lupus miliaris disseminatus faciei: A case report.

RATIONALE: Lupus miliaris disseminatus faciei (LMDF) is an inflammatory granulomatous skin disease without a clear etiology that frequently involves the middle area of the face and the upper eyelids. Pathological features of the disease include caseation necrosis and epithelioid granuloma. Consensus treatment for LMDF is currently unavailable. PATIENT CONCERNS: A 47-year-old Chinese female patient who presented with facial pruritic, erythematous papules 8 months before this study. She was diagnosed with skin tuberculosis at another hospital and given antituberculosis medication. However, the treatment was not efficacious. DIAGNOSES: In this study, the diagnosis of Demodex-induced LMDF was made by a dermatologist according to physical examination, skin biopsy pathology, and microscopic examination. INTERVENTIONS: The patient was given ornidazole tablets (500 mg twice a day) and recombinant bovine basic fibroblast growth factor gel (0.2 g/cm twice a day) for an 8-week period. OUTCOMES: Eight weeks after the treatment, the facial erythematous papules were improved, and no new skin lesions were observed. The patient showed no signs of recurrence during the 6-month follow-up. LESSONS SUBSECTIONS: This case showed that ornidazole combined with recombinant bovine basic fibroblast growth factor gel might be useful in treatment of Demodex-induced LMDF. In addition, the results suggested that pathological caseation necrosis was caused by a series of inflammatory and immune responses to Demodex infection.

Minimal Cerebrospinal Fluid Concentration of Miltefosine despite Therapeutic Plasma Levels during the Treatment of Amebic Encephalitis.

Miltefosine is an alkylphosphocholine compound that is used primarily for treatment of leishmaniasis and demonstrates in vitro and in vivo antiamebic activity against Acanthamoeba species. Recommendations for treatment of amebic encephalitis generally include miltefosine therapy. Data indicate that treatment with an amebicidal concentration of at least 16 µg/ml of miltefosine is required for most Acanthamoeba species. Although there is a high level of mortality associated with amebic encephalitis, a paucity of data regarding miltefosine levels in plasma and cerebrospinal fluid in vivo exists in the literature. We found that despite aggressive dosing (oral miltefosine 50 mg every 6 h) and therapeutic plasma levels, the miltefosine concentration in cerebrospinal fluid was negligible in a patient with AIDS and Acanthamoeba encephalitis.

Antimicrobial activities of green synthesized gums-stabilized nanoparticles loaded with flavonoids.

Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100-225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri, while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.

Dual 0.02% chlorhexidine digluconate - 0.1% disodium EDTA loaded thermosensitive ocular gel for Acanthamoeba keratitis treatment.

Poor bioavailability and low residence time limit the efficiency of conventional biguanide-based eye drops against Acanthamoeba keratitis. The aim of this work was to formulate an original anti-amoebic thermoreversible ocular gel combining biguanide and metalloproteases inhibitor - chelating agent. Chlorhexidine digluconate (CHX)-ethylenediaminetetraacetic acid disodium salt (Na2EDTA) were compounded in poloxamer 407 saline solution. 0.02% CHX - 0.1% Na2EDTA loaded thermosensitive ocular gel exhibited appropriate pH (5.73 ±â€¯0.06), iso-osmolality (314 ±â€¯5 mOsm/kg), viscosity (ranged between 15 and 25 mPa.s) and thermal gelation (26.5 °C and 33 °C) properties. Bioadhesion of gel was successfully tested onto isolated bovine eyes as well as the assessment of CHX penetration into the cornea. Intracorneal CHX concentration was found greater than trophozoite minimum amoebicidal concentration and minimal cysticidal concentration after 15-min and 2-h ocular exposure, respectively, while any CHX permeation through the cornea was detected (<51 ng/cm2/h). Improvement of CHX ocular bioavailability was attributed to probable solubilization of tear film lipid layer by poloxamer. In vitro efficiency of CHX-Na2EDTA ocular gel was confirmed from the drastic reduction of trophozoite and cyst survival (to 25% and 2%, respectively), confirming the potential of the multicomponent pharmaceutical material strategy for the treatment of Acanthamoeba keratitis.

Comparative study of tinidazole versus metronidazole in treatment of amebic liver abscess: A randomized control trial.

BACKGROUND: Metronidazole is a drug of choice for amebic liver abscess (ALA), but has long course and significant side effects. Thus, drugs like tinidazole with a better tolerability record need evaluation. METHODS: We conducted a randomized controlled trial at the Department of Gastroenterology, SMS Hospital, Jaipur, India. One hundred and fifty admitted patients were randomized into two treatment groups, metronidazole (group M, n = 75) and tinidazole (group T, n = 75). Patients were observed for clinical response, laboratory parameters, imaging, and side effects. Early clinical response (ECR) was defined as the absence of fever and abdominal pain within 72 h of treatment. Symptomatic clinical response (SCR) was defined as the absence of fever and abdominal pain irrespective of duration of treatment required. Follow up was done at 1, 3, and 6 months. RESULTS: ECR was 62.3% in group T vs. 37.7% in group M (p = 0.02). SCR was shorter in group T than group M (3.29 ± 1.61 days vs. 5.67 ± 2.93, p ≤ 0.001). Mean residual volume at the end of 1 month was lower in group T (130.7 ± 108.1 vs. 184.7 ± 143.3 mL, p = 0.01) and no significant difference was seen at 3 and 6 months. Tinidazole was better tolerated with fewer side effects. Low socioeconomic status, baseline abscess volume > 500 mL, hypoalbuminemia, pleural effusion, and history of ethanol use were associated with a late clinical response on univariate analysis of which low socioeconomic status was the only associated factor. CONCLUSION: Tinidazole, as compared to metronidazole, has early clinical response, shorter treatment course, favorable rate of recovery, and high tolerability; thus, tinidazole can be preferred over metronidazole in ALA.

Bioactivity, Safety, and Efficacy of Amphotericin B Nanomicellar Aerosols Using Sodium Deoxycholate Sulfate as the Lipid Carrier.

We report nanomicelles of amphotericin B (AmB) using various molar ratios of AmB and sodium deoxycholate sulfate (SDCS) for inhalation with improved stability, solubility, bioactivity, and safety. The particle sizes of all aerosolized formulations are expressed as mass median aerodynamic diameter (0.9-1.6 µm), fine particle fraction (70.3-86.5%), and geometric standard deviation (1.4-2.1) which indicated their sizes are appropriate for use as an inhaler. In vitro cytotoxicity studies conducted using respiratory and kidney cell lines demonstrated that the marketed Fungizone® was toxic to macrophage and embryonic kidney cells and cell viability decreased from 96 to 48% and from 97 to 67%, respectively when the AmB equivalent concentration was increased from 1 to 16 µg/mL. However, AmB-SDCS formulations showed no evidence of toxicity even up to 8 µg/mL compared to Fungizone®. Minimum inhibitory and fungicidal concentrations were significantly reduced against Cryptococcus neoformans, and Candida albicans. Also, antileishmanial activity significantly improved for AmB-SDCS formulations. There was an evidence of phagocytosis of the AmB-SDCS formulation by alveolar macrophages NR 8383. Molecular modeling studies suggested the role of hydrogen bonding in stabilization of the AmB-SDCS complex. This study indicated that AmB-SDCS nanomicelles can be used to design a safe and cost-effective AmB for inhalation. Graphical abstract ᅟ.

Acanthamoeba endophthalmitis during treatment for cutaneous disease in a renal transplant patient.

Acanthamoeba infections are difficult to diagnose and treat. We present a renal transplant patient who developed Acanthamoeba endophthalmitis on therapy with posaconazole and miltefosine for cutaneous acanthamobiasis. The patient was maintained on intracameral voriconazole injections, and oral azithromycin, fluconazole, and flucytosine. This case highlights novel presentations and treatments for acanthamoebic infection.

Diloxanide furoate binary complexes with ß-, methyl-ß-, and hydroxypropyl-ß-cyclodextrins: inclusion mode, characterization in solution and in solid state and in vitro dissolution studies.

The purpose of this study was to investigate the effect on solubility and dissolution rate of binary complexes of ß-(ßCD), methyl-(MßCD) and hydroxypropyl-ß-cyclodextrin (HPßCD) with diloxanide furoate (DF). The complexation in solution was evaluated by phase solubility studies and 1H nuclear magnetic resonance (NMR). Enhanced water solubility of DF was obtained with the DF:MßCD system (61-fold). The mode of inclusion was supported by NMR experiments, which indicated that real inclusion complexes were formed between DF and MßCD or HPßCD. Solid state analysis was performed using infrared and thermal methods, which suggested the formation of true inclusion complexes of DF with two derivatized cyclodextrins, MßCD and HPßCD, and an exclusion complex with ßCD when the systems were prepared by freeze-dried technique. Dissolution studies conducted in simulated gastric fluid (2 h) and subsequent simulated intestinal fluid (next 4 h) showed increased dissolution rate of DF from the freeze-dried systems with ßCD, MßCD, and HPßCD (85; 77 and 75% of dissolved drug at 5 min, respectively) and 100% of the drug dissolved at 150 min for the three systems. The enhancement of the solubility and the dissolution of DF observed make these complexes promising candidates for the preparation of oral pharmaceutical formulations.

Brain-Eating Amoebae: Silver Nanoparticle Conjugation Enhanced Efficacy of Anti-Amoebic Drugs against Naegleria fowleri.

The overall aim of this study was to determine whether conjugation with silver nanoparticles enhances effects of available drugs against primary amoebic meningoencephalitis due to Naegleria fowleri. Amphotericin B, Nystatin, and Fluconazole were conjugated with silver nanoparticles, and synthesis was confirmed using UV-visible spectrophotometry. Atomic force microscopy determined their size in range of 20-100 nm. To determine amoebicidal effects, N. fowleri were incubated with drugs-conjugated silver nanoparticles, silver nanoparticles alone, and drugs alone. The findings revealed that silver nanoparticles conjugation significantly enhanced antiamoebic effects of Nystatin and Amphotericin B but not Fluconazole at micromolar concentrations, compared with the drugs alone. For the first time, our findings showed that silver nanoparticle conjugation enhances efficacy of antiamoebic drugs against N. fowleri. Given the rarity of the disease and challenges in developing new drugs, it is hoped that modifying existing drugs to enhance their antiamoebic effects is a useful avenue that holds promise in improving the treatment of brain-eating amoebae infection due to N. fowleri.

Evaluation of In Vitro Antiamoebic Activity of Antimicrobial Agents Against Clinical Acanthamoeba Isolates.

PURPOSE: The aim of this study was to elucidate in vitro antiamoebic activity of antimicrobial agents at short exposure times similar to those used for actual treatment against Acanthamoeba strains isolated from patients with keratitis. METHODS: The 5 clinical Acanthamoeba isolated in Japan were used in this study. Identification of genotypes for the Acanthamoeba isolates was performed using partial 18S ribosomal DNA (rDNA), including the ASA.S1 region sequences. Fluconazole, miconazole, itraconazole, voriconazole, amphotericin B, natamycin (pimaricin), and micafungin (antifungal agents), and chlorhexidine (a biguanide disinfectant), and sulfamethoxazole and paromomycin (antibacterial agents) were used to determine the antiamoebic activity against Acanthamoeba, which were determined by 50% and 90% growth inhibitory concentrations (IC50 and IC90) following exposing to each drug at 25°C for 7 days and 12 h. RESULTS: Among the tested antimicrobial agents, natamycin strongly inhibited the growth of all Acanthamoeba isolates at low concentration in both the 7-day (IC90 = 4.1 µg/mL) and 12-h (IC90 = 11.6 µg/mL) assays. Additionally, sulfamethoxazole exhibited strong antiamoebic activity (IC90 = 9.8 µg/mL) at low concentration in the 7-day assay. CONCLUSIONS: Our findings showed that natamycin ophthalmic solution might be an effective agent against Acanthamoeba keratitis. Additionally, frequent administration of sulfamethoxazole ophthalmic solution or systemic sulfamethoxazole-trimethoprim is also considered as an effective treatment for Acanthamoeba keratitis.

Disseminated Acanthamoeba infection in a heart transplant recipient treated successfully with a miltefosine-containing regimen: Case report and review of the literature.

Disseminated acanthamoebiasis is a rare, often fatal, infection most commonly affecting immunocompromised patients. We report a case involving sinuses, skin, and bone in a 60-year-old woman 5 months after heart transplantation. She improved with a combination of flucytosine, fluconazole, miltefosine, and decreased immunosuppression. To our knowledge, this is the first case of successfully treated disseminated acanthamoebiasis in a heart transplant recipient and only the second successful use of miltefosine for this infection among solid organ transplant recipients. Acanthamoeba infection should be considered in transplant recipients with evidence of skin, central nervous system, and sinus infections that are unresponsive to antibiotics. Miltefosine may represent an effective component of a multidrug therapeutic regimen for the treatment of this amoebic infection.

Identification and Characterization of the Human Cytosolic Sulfotransferases Mediating the Sulfation of Clioquinol and Iodoquinol.

OBJECTIVE: The aim of the current study was to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating clioquinol and iodoquinol, and to verify the presence of clioquinol/ iodoquinol-sulfating activity in human organ homogenates and cultured cells. METHOD: An established sulfotransferase assay was employed to analyze clioquinol/iodoquinolsulfating activity of thirteen known human SULTs, as well as cytosols of human kidney, liver, lung, and small intestine. Metabolic labeling with [35S]sulfate in the presence of different concentrations of clioquinol/iodoquinol was performed using cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells. RESULTS: A systematic analysis revealed that six of the thirteen known human SULTs, SULT1A1 SULT1A2, SULTA3, SULT1B1, SULT1C4, and SULT1E1 showed considerable clioquinol/ iodoquinol-sulfating activity. Kinetic parameters of the sulfation of clioquinol and iodoquinol by three SULTs, SULT1A1, SULT1A3, and SULT1C4, that showed the strongest clioquinol/iodoquinolsulfating activity were determined. Moreover, clioquinol/iodoquinol-sulfating activity was detected in the cytosol fractions of human liver, lung, kidney, and small intestine. Cultured HepG2 and Caco-2 cells were shown to be capable of sulfating clioquinol/iodoquinol under metabolic conditions. CONCLUSION: Collectively, these results provided a molecular basis underling the metabolism of clioquinol and iodoquinol through sulfation.

The use of dimethyl sulfoxide in contact lens disinfectants is a potential preventative strategy against contracting Acanthamoeba keratitis.

Acanthamoeba castellanii is the causative agent of blinding keratitis. Though reported in non-contact lens wearers, it is most frequently associated with improper use of contact lens. For contact lens wearers, amoebae attachment to the lens is a critical first step, followed by amoebae binding to the corneal epithelial cells during extended lens wear. Acanthamoeba attachment to surfaces (biological or inert) and migration is an active process and occurs during the trophozoite stage. Thus retaining amoebae in the cyst stage (dormant form) offers an added preventative measure in impeding parasite traversal from the contact lens onto the cornea. Here, we showed that as low as 3% DMSO, abolished A. castellanii excystation. Based on the findings, it is proposed that DMSO should be included in the contact lens disinfectants as an added preventative strategy against contracting Acanthamoeba keratitis.

Enhancement of site specific delivery of diloxanide furoate as an antiamoebic drug.

The basic aim of the present research work is to deliver the diloxanide furoate (DF) at specific area using pectin microspheres. The microspheres were prepared by spray drying method and cross-linked by zinc acetate. Different concentrations of polymer (pectin 0.5-3%) and cross-linking agent (0-3% w/v in a mixture of ethanol:water) are taken to optimize the entrapment efficiency, swelling behavior, size and first 6h in-vitro release in simulated gastric fluids. Optimized formulation was characterized in the terms of in-vitro release, in-vivo drug disposition in various organs and in the blood of Sprague-Dawley albino rats and in-vivo gastrointestinal tract transit behavior using X-ray imaging method on albino rabbits. Findings suggested that microspheres containing a concentration of polymer (2% w/v) have average size of 100-500 µm, entrapment efficiency 85.82 ± 0.5 with swelling index 18.77 ± 5.21. In-vitro results and in-vivo gastric transit behavior (using X-ray imaging) have shown no release in first 3-6h that proved the colon specific delivery of DF. The results also suggested that the above approach have not only site specific delivery, but it improves the conversion of active drug by increasing the enzyme mediated hydrolytic degradation of DF due to the presence of polysaccharide polymer:water gel complex.

Cervical amoebiasis mimicking cervical carcinoma: A rare presentation of a common infection.

Cervical amoebiasis is an extremely rare diagnosis with only a small number of published case reports. This disease may present as cervical growth mimicking cervical carcinoma. Owing to the similarity of the clinical presentation of bleeding per vagina and per speculum examination showing growth or ulcers, definitive diagnosis is made on microscopic examination only. We present a rare case of cervical amoebiasis in a 28-year-old, multiparous female who presented with a history of vaginal bleeding. The patient was treated with metronidazole and diloxanide furate, after which she recovered. Awareness of this rare entity is important for clinical suspicion and for the pathologist to identify trophozoites and make a diagnosis, preventing unwarranted investigations. Accurate diagnosis also facilitates quick management of a patient; as this disease is an infective pathology that can easily be treated by antibiotics.

Targeting cyst wall is an effective strategy in improving the efficacy of marketed contact lens disinfecting solutions against Acanthamoeba castellanii cysts.

Acanthamoeba cysts are highly resistant to contact lens disinfecting solutions. Acanthamoeba cyst wall is partially made of 1,4 ß-glucan (i.e., cellulose) and other complex polysaccharides making it a hardy shell that protects the resident amoeba. Here, we hypothesize that targeting the cyst wall structure in addition to antiamoebic compound would improve the efficacy of marketed contact lens disinfecting solutions. Using chlorhexidine as an antiamoebic compound and cellulase enzyme to disrupt cyst wall structure, the findings revealed that combination of both agents abolished viability of Acanthamoeba castellanii cysts and trophozoites. When tested alone, none of the agents nor contact lens disinfecting solutions completely destroyed A. castellanii cysts and trophozoites. The absence of cyst wall-degrading enzymes in marketed contact lens disinfecting solutions render them ineffective against Acanthamoeba cysts. It is concluded that the addition of cyst wall degrading molecules in contact lens disinfecting solutions will enhance their efficacy in decreasing the incidence of Acanthamoeba effectively.

Assessment of blood-brain barrier penetration of miltefosine used to treat a fatal case of granulomatous amebic encephalitis possibly caused by an unusual Balamuthia mandrillaris strain.

Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 µg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 µg/mL. These are the first results confirming some blood-brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug's toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.

Acanthamoeba keratitis: clinical characteristics and management.

PURPOSE: To review characteristics of clinical features in 260 eyes with Acanthamoeba keratitis (AK) from 1991 to 2013. METHODS: We retrospectively analyzed 260 eyes from 259 patients diagnosed with Acanthamoeba keratitis (AK) by smear and/or culture and/or laser confocal microscopy between 1991 and 2013 at Beijing Tongren Eye Center. Patient data included age, gender, profession, predisposing risk factors, clinical presentation, treatment, therapy effect, and course of disease. RESULTS: The most common risk factor in this study was ocular trauma (53.1%), followed by contact lens wear (29.8%). Most of the AK patients were farmers (50.8%), and students (23.8%) formed the second largest group of AK patients. Most cases (77.8%) were classified as advanced stage AK at initial presentation; only a few patients (5.6%) were diagnosed with early stage disease. Of 90 cases, 77 (85.6%) had salt-like dense infiltrate dots on the corneal ulcer, 54 cases (61.1%) had groove-shaped corneal melting around the corneal ulcer, and 37 cases(41.1%) had classic ring infiltrate. Nine cases experienced improved conditions at the beginning of treatment, which subsequently worsened, and then improved gradually. Treatments were administered according to the disease stage. After topical anti-amoeba drug therapy, 48 of 90 cases (53.3%) were cured with corneal scarring remaining; mean duration of treatment was 5 months. CONCLUSION: Salt-like dense infiltrate dots and groove-shaped corneal melting may serve as useful clues in the diagnosis of AK, in addition to radial neuritis and ring infiltration. Some patients with AK may experience a worsened condition after early improvement with anti-amoeba drug therapy, and then improve gradually.