Successful medical management of Pythium insidiosum keratitis using a combination of minocycline, linezolid, and chloramphenicol

Abstract

Purpose To report successful medical management of Pythium insidiosum keratitis using an antibiotic combination of minocycline, linezolid, and chloramphenicol. Observations A 20-year-old Japanese man was referred for visual disturbance, hyperemia, and discharge from his right eye. Slit-lamp examination revealed a paracentral corneal hyphate ulcer. His visual acuity was 20/28. Smear examination of corneal scrapings revealed a filamentous fungus. Pimaricin ointment four times a day and voriconazole eye drops hourly were initially prescribed. Although intravenous liposomal amphotericin B 100 mg was added, the corneal infiltrates and ulcer worsened. The possibility of P. insidiosum keratitis was considered, and in vitro antifungal susceptibility testing were performed based on the disc diffusion method. The inhibition zones around each antibiotic disc revealed that the pathogen was susceptible to minocycline, linezolid, and chloramphenicol. Therefore, minocycline ointment four times a day, chloramphenicol eye drops hourly, and linezolid 1200 mg orally per day were also administered. Eventually, sequencing of ribosomal DNA confirmed the pathogen to be P. insidiosum . The triple regimen dramatically improved the patient's keratitis. Therapeutic penetrating keratoplasty for corneal perforation was successfully performed, and his visual acuity recovered from 20/2000 to 20/25. Conclusions and importance We have encountered a case of P. insidiosum keratitis that responded to a combination of minocycline, linezolid, and chloramphenicol. This triple combination should be considered in patients with P. insidiosum keratitis.

Clinical Characteristics, Histopathology, and Treatment Outcomes of Pythium Keratitis: A Retrospective Cohort Study

“…1 The authors concluded that there was still a knowledge gap regarding the best treatment because conventional antifungal agents are not effective against P. insidiosum. Newer treatments such as linezolid, azithromycin, and PIAI were reported to be successful in healing the infection in small case series 8,16 and in vitro susceptibility testing. 22 Currently, TPK remains the most effective treatment but has to be done as early as possible.…”

“…14 Recently, some Pythium keratitis cases were successfully treated with antibiotics, such as minocycline, azithromycin, chloramphenicol, and linezolid. 1,15,16 There is no standard treatment regimen for Pythium keratitis to date, but most of the patients undergo early therapeutic penetrating keratoplasty (TPK). 11 Pythium antigen immunotherapy (PIAI) has also been studied, but its efficacy remains controversial.…”

Recent update in diagnosis and treatment of human pythiosis

“…An extensive and aggressive infiltration of P . insidiosum could result in corneal perforation, anterior chamber, limbal and scleral invasions, or endophthalmitis in a few days or weeks (Lekhanont et al, 2009;Lelievre et al, 2015;Rathi et al, 2018;Agarwal et al, 2019;Badenoch et al, 2001;He et al, 2016;Maeno et al, 2019;Ros Castellar et al, 2017;Thanathanee et al, 2013;Sharma et al, 2015;Agarwal et al, 2018).…”

“…Potential risk factors for pythiosis include farming exposure, direct contact with a water resource (i.e., lake, river, lagoon, swamp, or even swimming pool), and a history of travel to endemic countries, such as Thailand (Krajaejun et al, 2006b;Lelievre et al, 2015;Hasika et al, 2019;Appavu, Prajna & Rajapandian, 2019). Inappropriate hygiene of contact lens can pose a risk (Lekhanont et al, 2009;Lelievre et al, 2015;Badenoch et al, 2001;Maeno et al, 2019;Bernheim et al, 2019;Tanhehco et al, 2011;Barequet, Lavinsky & Rosner, 2013;Neufeld et al, 2018;Raghavan et al, 2018), and exposure to dust or some foreign body in their eyes (Bagga et al, 2018;Hasika et al, 2019) predisposes individuals with no agricultural activity to this infection. The incidence of pythiosis follows a seasonal trend (Hasika et al, 2019;Thanathanee et al, 2013) with outbreaks of Pythium keratitis occurring during the rainy season in Thailand (Thanathanee et al, 2013) and around June to September during monsoon season in South India (Hasika et al, 2019).…”

“…The first patient with presumptive Pythium keratitis was successfully managed non-surgically with a triple regimen, consisting of topical 0.2% linezolid every hour, topical 1% azithromycin every 2 h, and oral azithromycin 500 mg once daily for 3 days a week (Ramappa et al, 2017). One presumptive case and two confirmed cases of Pythium keratitis were successfully treated with similar regimens, including a combination of topical and oral azithromycin and topical voriconazole, a combination of topical minocycline and chloramphenicol and oral linezolid, and a combination of oral doxycycline and clindamycin and topical azithromycin, respectively (Chatterjee & Agrawal, 2018;Maeno et al, 2019;Bernheim et al, 2019). Intracameral injection and oral minocycline have also been used along with repeated keratoplasty to successfully treat a patient with recurrent infection after the second corneal transplant (Ros Castellar et al, 2017).…”