Role of Topical Ethanol in the Treatment of Pythium insidiosum Keratitis—A Proof of Concept

Agarwal, Shweta; Srinivasan, Bhaskar; Janakiraman, Narayanan; Therese, Lily; Krishnakumar, Subramanian; Patel, Nilay; Thenmozhi,; Iyer, Geetha

doi:10.1097/ico.0000000000002370

Cited by 10 publications

(16 citation statements)

References 17 publications

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“…As mentioned above, Thailand and India accounted for the highest prevalence of pythiosis in humans (Table 2). Surges of human cases (all had ocular pythiosis) were published by several Indian medical centers during the last six years (2015-2021; Figure 2) [50,59,105,122,[179][180][181][182][183][184][185][186][187][188], leading India to report the highest case number of human pythiosis so far. Surprisingly, no vascular pythiosis was diagnosed in India, while almost all patients with this disease type (99.4%) were detected in Thailand.…”

Section: Discussionmentioning

confidence: 99%

Global Distribution and Clinical Features of Pythiosis in Humans and Animals

Yolanda

Krajaejun

2022

JoF

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Pythiosis is a difficult-to-treat infectious disease caused by Pythium insidiosum. The condition is unfamiliar among healthcare workers. Manifestation of pythiosis is similar to other fungal infections, leading to misdiagnosis and delayed treatment. The geographical extent of pythiosis at a global scale is unclear. This study aimed to analyze the clinical information recorded in the scientific literature to comprehensively project epidemiological characteristics, clinical features, and future trends of pythiosis. From 1980 to 2021, 4203 cases of pythiosis in humans (n = 771; 18.3%) and animals (primarily horse, dog, and cow; n = 3432; 81.7%), with an average of 103 cases/year, were recruited. Pythiosis case reports significantly increased in the last decade. Pythiosis spanned 23 tropical, subtropical, and temperate countries worldwide. Some patients acquired pythiosis from a trip to an endemic country. Strikingly, 94.3% of human cases were in India and Thailand, while 79.2% of affected animals were in the U.S.A. and Brazil. Clinical features of pythiosis varied. Vascular and ocular pythiosis were only observed in humans, whereas cutaneous/subcutaneous and gastrointestinal infections were predominant in animals. Mortality depended on host species and clinical forms: for example, none in patients with ocular pythiosis, 0.7% in cows with a cutaneous lesion, 26.8% in humans with vascular disease, 86.4% in dogs with gastrointestinal pathology, and 100% in several animals with disseminated infection. In summary, this study reports up-to-date epidemiological and clinical features of pythiosis in humans and animals. It increases awareness of this life-threatening disease, as the illness or outbreak can exist in any country, not limited to the endemic areas.

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Section: Discussionmentioning

confidence: 99%

Global Distribution and Clinical Features of Pythiosis in Humans and Animals

Yolanda

Krajaejun

2022

JoF

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“…On comparing the characteristic features, eyes with infiltrates > 6 mm, longer duration, and posterior stromal involvement did not respond to medical therapy being constituted by a combination of topical linezolid, azithromycin, and oral azithromycin. The authors recommend initiating medical treatment in mild-to-moderate cases, and therapeutic keratoplasty (TPK) can be planned based on the treatment [ 68 ]. In another series of 18 eyes from Eastern India, all seven eyes where medical therapy was initiated ended up requiring a therapeutic graft or were eviscerated [ 28 ].…”

Section: Microbiological Laboratory Diagnosismentioning

confidence: 99%

“…An improved understanding of the cell wall structure and organization will further open new avenues to be explored in managing this refractory organism. A summary of review of literature of all the clinical studies and case reports or PI keratitis is listed in Table 2 [ 3 , 8 , 10 , 12 , 15 – 19 , 22 – 29 , 32 – 34 , 38 , 68 , 75 – 85 ].…”

Section: Future Directionsmentioning

confidence: 99%

Pythium insidiosum Keratitis: Past, Present, and Future

et al. 2022

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Pythium insidiosum (PI) is an oomycete, a protist belonging to the clade Stramenopila. PI causes vision-threatening keratitis closely mimicking fungal keratitis (FK), hence it is also labeled as “parafungus”. PI keratitis was initially confined to Thailand, USA, China, and Australia, but with growing clinical awareness and improvement in diagnostic modalities, the last decade saw a massive upsurge in numbers with the majority of reports coming from India. In the early 1990s, pythiosis was classified as vascular, cutaneous, gastrointestinal, systemic, and ocular. Clinically, morphologically, and microbiologically, PI keratitis closely resembles severe FK and requires a high index of clinical suspicion for diagnosis. The clinical features such as reticular dot infiltrate, tentacular projections, peripheral thinning with guttering, and rapid limbal spread distinguish it from other microorganisms. Routine smearing with Gram and KOH stain reveals perpendicular septate/aseptate hyphae, which closely mimic fungi and make the diagnosis cumbersome. The definitive diagnosis is the presence of dull grey/brown refractile colonies along with zoospore formation upon culture by leaf induction method. However, culture is time-consuming, and currently polymerase chain reaction (PCR) method is the gold standard. The value of other diagnostic modalities such as confocal microscopy and immunohistopathological assays is limited due to cost, non-availability, and limited diagnostic accuracy. PI keratitis is a relatively rare disease without established treatment protocols. Because of its resemblance to fungus, it was earlier treated with antifungals but with an improved understanding of its cell wall structure and absence of ergosterol, this is no longer recommended. Currently, antibacterials have shown promising results. Therapeutic keratoplasty with good margin (1 mm) is mandated for non-resolving cases and corneal perforation. In this review, we have deliberated on the evolution of PI keratitis, covered all the recently available literature, described our current understanding of the diagnosis and treatment, and the potential future diagnostic and management options for PI keratitis.

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“…[ 122 ] Recently, the safety and efficacy profile of topical ethanol in the treatment of Pythium keratitis was reported; however, the exact dose and strength of ethanol that will be most effective needs further work. [ 123 ]…”

Section: Antimicrobialsmentioning

confidence: 99%

“…[ 158 ] Agarwal et al . [ 123 ] reported the efficacy and safety of topical absolute ethanol in the treatment of Pythium insidiosum keratitis. They noted that the absence of ergosterol in the cell wall of Pythium makes it more susceptible to ethanol as compared to fungi in in vitro studies.…”

Section: Antimicrobialsmentioning

confidence: 99%

Update on diagnosis and management of refractory corneal infections

Agarwal

Khan

Vanathi

et al. 2022

Indian Journal of Ophthalmology

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Infectious keratitis is a medical emergency resulting in significant visual morbidity. Indiscriminate use of antimicrobials leading to the emergence of resistant or refractory microorganisms has further worsened the prognosis. Coexisting ocular surface diseases, delay in diagnosis due to inadequate microbiological sample, a slow-growing/virulent organism, or systemic immunosuppressive state all contribute to the refractory response of the ulcer. With improved understanding of these varied ocular and systemic factors contributing to the refractory nature of the microbes, role of biofilm formation and recent research on improving the bioavailability of drugs along with the development of alternative therapies have helped provide the required multidimensional approach to effectively diagnose and manage cases of refractory corneal ulcers and prevent corneal perforations or further dissemination of disease. In this review, we explore the current literature and future directions of the diagnosis and treatment of refractory keratitis.

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Role of Topical Ethanol in the Treatment of Pythium insidiosum Keratitis—A Proof of Concept

Cited by 10 publications

References 17 publications

Global Distribution and Clinical Features of Pythiosis in Humans and Animals

Global Distribution and Clinical Features of Pythiosis in Humans and Animals

Pythium insidiosum Keratitis: Past, Present, and Future

Update on diagnosis and management of refractory corneal infections

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