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Parasitology Research Dec 2023The members of genus Acanthamoeba are the etiological agent of uncommon but severe or even fatal opportunistic infections in human beings. The presence of different... (Review)
Review
The members of genus Acanthamoeba are the etiological agent of uncommon but severe or even fatal opportunistic infections in human beings. The presence of different classes of intracellular and extracellular proteases including serine proteases, cysteine proteases, and metalloproteases has been well documented in environmental and clinical isolates of Acanthamoeba spp. However, the role of the proteolytic enzymes in physiological, biological, and pathological mechanisms of the amoeba remains partially investigated. Some attempts have been conducted using various methods to determine the profile of proteases (number, class, optimal conditions, and activity of the enzymes), and possible pathogenicity mechanism of the proteolytic enzymes (various protein substrate degradation, cytopathic effect on different cell lines). In some cases, it was attempted to correlate intracellular and extracellular protease profile with pathogenicity potential of strains. This review revealed that the protease profile of different strains of Acanthamoeba was extremely complex, therefore, further comprehensive studies with application of a combination of various methods may help to elucidate the role of the enzymes.
Topics: Humans; Acanthamoeba; Serine Proteases; Serine Endopeptidases; Acanthamoeba Keratitis; Cell Line
PubMed: 38063887
DOI: 10.1007/s00436-023-08059-z -
Ophthalmology Mar 2024To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK)... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml)+ propamidine 0.1% (1 mg/ml) with PHMB 0.08% (0.8 mg/ml)+ placebo (PHMB 0.08%) for Acanthamoeba keratitis (AK) treatment.
DESIGN
Prospective, randomized, double-masked, active-controlled, multicenter phase 3 study (ClinicalTrials.gov identifier, NCT03274895).
PARTICIPANTS
One hundred thirty-five patients treated at 6 European centers.
METHODS
Principal inclusion criteria were 12 years of age or older and in vivo confocal microscopy with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis who were using topical steroids and antiviral and antifungal drugs before randomization. Principal exclusion criteria were concurrent herpes or fungal keratitis and use of antiamebic therapy (AAT). Patients were randomized 1:1 using a computer-generated block size of 4. This was a superiority trial having a predefined noninferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20-percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (MCR; without surgery or change of AAT) within 12 months, cure defined by clinical criteria 90 days after discontinuing anti-inflammatory agents and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes.
MAIN OUTCOME MEASURES
The main outcome measure was MCR within 12 months, with secondary outcomes including best-corrected visual acuity and treatment failure rates. Safety outcomes included adverse event rates.
RESULTS
One hundred thirty-five participants were randomized, providing 127 in the full-analysis subset (61 receiving PHMB 0.02%+ propamidine and 66 receiving PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR within 12 months was 86.6% (unadjusted, 88.5%) for PHMB 0.02%+ propamidine and 86.7% (unadjusted, 84.9%) for PHMB 0.08%; the noninferiority requirement for PHMB 0.08% was met (adjusted difference, 0.1 percentage points; lower one-sided 95% confidence limit, -8.3 percentage points). Secondary outcomes were similar for both treatments and were not analyzed statistically: median best-corrected visual acuity of 20/20 and an overall treatment failure rate of 17 of 127 patients (13.4%), of whom 8 of 127 patients (6.3%) required therapeutic keratoplasty. No serious drug-related adverse events occurred.
CONCLUSIONS
PHMB 0.08% monotherapy may be as effective (or at worse only 8 percentage points less effective) as dual therapy with PHMB 0.02%+ propamidine (a widely used therapy) with medical cure rates of more than 86%, when used with the trial treatment delivery protocol in populations with AK with similar disease severity.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Acanthamoeba Keratitis; Benzamidines; Biguanides; Orphan Drug Production; Prospective Studies
PubMed: 37802392
DOI: 10.1016/j.ophtha.2023.09.031 -
Cornea Nov 2023To summarize the evidence base on the use of topical corticosteroids for infectious keratitis. (Review)
Review
PURPOSE
To summarize the evidence base on the use of topical corticosteroids for infectious keratitis.
METHODS
Narrative review.
RESULTS
Infectious keratitis is a painful condition that often results in visually significant corneal stromal scarring, even when antimicrobial therapy is successful. Corticosteroids may reduce inflammation and subsequent scar formation and while relieving the acute ocular pain associated with a corneal ulcer. However, corticosteroids also reduce the host immune response, which could hinder the ability to clear infection. The safety and effectiveness of corticosteroids depends to a large part on the efficacy of the antimicrobials being used to treat the underlying infection. Randomized trials have found that corticosteroids are safe and effective for herpetic keratitis when used with appropriate antiviral therapy, and are safe for bacterial keratitis when used with broad spectrum topical antibiotics. The effectiveness of corticosteroids for bacterial keratitis has not been shown conclusively, although more advanced bacterial corneal ulcers may do better with corticosteroids. No randomized trials have assessed the safety and effectiveness of steroids for fungal or acanthamoeba keratitis. Animal studies suggest corticosteroids may be harmful in fungal keratitis, and observational human studies have found that steroids are harmful for fungal and acanthamoeba keratitis when started prior to anti-amoebics.
CONCLUSIONS
Topical corticosteroids, when used as an adjunct to antimicrobial therapy, may be beneficial if the antimicrobial being used can effectively clear or suppress the infection, such as in bacterial and herpetic keratitis. Randomized trials would be helpful to further delineate the role of corticosteroids for infectious keratitis.
Topics: Humans; Acanthamoeba Keratitis; Corneal Ulcer; Keratitis, Herpetic; Adrenal Cortex Hormones; Glucocorticoids; Eye Infections, Bacterial; Steroids; Anti-Bacterial Agents
PubMed: 38112645
DOI: 10.1097/ICO.0000000000003340 -
Journal of Basic Microbiology Apr 2024Free-living amoebae of the genus Acanthamoeba are infected by various bacteria in nature, and thus bacteria can protect themselves from adverse environmental conditions....
Free-living amoebae of the genus Acanthamoeba are infected by various bacteria in nature, and thus bacteria can protect themselves from adverse environmental conditions. Contrary to this ameba-bacteria relationship whether Acanthamoeba has antibacterial effects on bacteria is the different aspect of the relationship between these microorganisms. In this study, we investigate various Acanthamoeba strains have antibacterial effects on various Staphylococcus strains. Three environmental Acanthamoeba strains, isolated from various aquatic environments in Turkey, and Acanthamoeba castellanii ATCC 50373 standard strains were used in the study. The antistaphylococcal effect of cell-free supernatant (CFS) obtained from these amoebae against 12 different Staphylococcus bacteria was investigated by colony counting method. In addition, the pathogenicity of the tested Acanthamoeba strains was determined using osmotolerance and thermotolerance tests. CFSs obtained from Acanthamoeba were found to have varying degrees of antistaphylococcal effects on various Staphylococcus strains (0%-100%). It was determined that the CFS of the standard Acanthamoeba strain showed 100% inhibitory effect against one clinical methicillin-resistant Staphylococcus aureus strain (M2). Also, CFS of Ugöl strain showed 99.97% inhibitory effect against one clinical methicillin-sensitive Staphylococcus epidermidis strain (L3). It was determined that all Acanthamoeba isolates had no pathogenic potential. According to the results, it has been observed that Acanthamoeba produces antibacterial substance(s) against Staphylococcus bacteria and that the ameba-bacteria relationship may also result in the detriment of the bacteria. Furthermore, the current study indicates that new and natural antimicrobial agents from Acanthamoeba can be used as an alternative to infections caused by Staphylococcus.
Topics: Staphylococcus; Methicillin-Resistant Staphylococcus aureus; Acanthamoeba castellanii; Anti-Infective Agents; Anti-Bacterial Agents; Bacteria
PubMed: 38416601
DOI: 10.1002/jobm.202300551 -
Diagnostics (Basel, Switzerland) Aug 2023keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is... (Review)
Review
keratitis (AK) is a painful and sight-threatening parasitic corneal infection. In recent years, the incidence of AK has increased. Timely and accurate diagnosis is crucial during the management of AK, as delayed diagnosis often results in poor clinical outcomes. Currently, AK diagnosis is primarily achieved through a combination of clinical suspicion, microbiological investigations and corneal imaging. Historically, corneal scraping for microbiological culture has been considered to be the gold standard. Despite its technical ease, accessibility and cost-effectiveness, the long diagnostic turnaround time and variably low sensitivity of microbiological culture limit its use as a sole diagnostic test for AK in clinical practice. In this review, we aim to provide a comprehensive overview of the diagnostic modalities that are currently used to diagnose AK, including microscopy with staining, culture, corneal biopsy, in vivo confocal microscopy, polymerase chain reaction and anterior segment optical coherence tomography. We also highlight emerging techniques, such as next-generation sequencing and artificial intelligence-assisted models, which have the potential to transform the diagnostic landscape of AK.
PubMed: 37627913
DOI: 10.3390/diagnostics13162655 -
Biology Dec 2023Keratitis (AK) is a severe corneal infection caused by the species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and... (Review)
Review
Keratitis (AK) is a severe corneal infection caused by the species of protozoa, potentially leading to permanent vision loss. AK requires prompt diagnosis and treatment to mitigate vision impairment. Diagnosing AK is challenging due to overlapping symptoms with other corneal infections, and treatment is made complicated by the organism's dual forms and increasing virulence, and delayed diagnosis. In this review, new approaches in AK diagnostics and treatment within the last 5 years are discussed. The English-language literature on PubMed was reviewed using the search terms " keratitis" and "diagnosis" or "treatment" and focused on studies published between 2018 and 2023. Two hundred sixty-five publications were initially identified, of which eighty-seven met inclusion and exclusion criteria. This review highlights the findings of these studies. Notably, advances in PCR-based diagnostics may be clinically implemented in the near future, while antibody-based and machine-learning approaches hold promise for the future. Single-drug topical therapy (0.08% PHMB) may improve drug access and efficacy, while oral medication (i.e., miltefosine) may offer a treatment option for patients with recalcitrant disease.
PubMed: 38132315
DOI: 10.3390/biology12121489 -
Indian Journal of Ophthalmology Apr 2024This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical... (Review)
Review
This is a comprehensive review after a thorough literature search in PubMed-indexed journals, incorporating current information on the pathophysiology, clinical features, diagnosis, medical and surgical therapy, as well as outcomes of Acanthamoeba keratitis (AK). AK is a significant cause of ocular morbidity, and early diagnosis with timely institution of appropriate therapy is the key to obtaining good outcomes. The varied presentations result in frequent misdiagnosis, and co-infections can increase the morbidity of the disease. The first line of therapy continues to be biguanides and diamidines, with surgery as a last resort.
Topics: Humans; Acanthamoeba Keratitis; Pentamidine; Biguanides
PubMed: 38454853
DOI: 10.4103/IJO.IJO_2627_23