Post-Keratoplasty Infectious Keratitis Caused by

Background

Infectious keratitis may be caused by bacteria, fungi, viruses, parasites, or a polymicrobial infection [1]. There is an increased risk of microbial keratitis following penetrating keratoplasty. The incidence of microbial keratitis after optical penetrating keratoplasty varies from 1.76% to 7.4% in developed countries and from 11.9% to 25% in developing countries [2]. Post-keratoplasty infectious keratitis is a diagnostic and therapeutic challenge. Bacteria have been reported to be the most common causative agents of infectious keratitis, with Staphylococcus epidermidis being the most commonly isolated organism [1,3]. Common risk factors for post-keratoplasty infectious keratitis include previous corneal infection, persistent epithelial defects, ocular surface disorders, suture-related problems, and the use of topical corticosteroids [1,3]. In the past 10 years, ocular prostheses have been introduced as a cosmetic solution for patients after enucleation. It is well known that the presence of an ocular prosthesis predisposes patients to inflammation or infection by affecting the ocular surface and causing disruption of the ocular microbiome which predisposes the ocular surface to infection [4]. Risk factors which predispose patients to develop an infection of the ocular prosthesis include compromised ocular surface, micro-biome dysbiosis, biofilm formation, chronic use of low-dose antibiotics or steroids, and prosthetic cleaning regimens [4]. We present a case of a single-eye patient who developed microbial keratitis in his seeing eye. The source of the infection was found to be the orbital socket of the fellow eye. Culture results from both eyes were positive for a rare gram-negative organism, Elizabethkingia meningoseptica.

Case Report

A 73-year-old man presented to the outpatient clinic during a routine followup in June 2021. On presentation, the patient complained of a sudden decrease of vision in his left eye for the duration of 2 months. The right eye had been enucleated during childhood due to ocular trauma and an ocular prosthesis was placed in the socket. The patient had undergone optical penetrating keratoplasty 30 years ago due to a trachomatous scar. He had undergone combined extracapsular cataract extraction, posterior chamber intraocular lens implantation, and penetrating keratoplasty for mature cataract and for a failed graft that was performed in February of 2016. The medical history of the patient was negative. On examination, the visual acuity of the left eye was 20/200. The intraocular pressure of the left eye was 12 mmHg. Anterior segment examination of the left eye showed diffuse graft edema and inferior graft infiltrate involving the anterior stroma measuring 1.5×2 mm with an overlying corneal epithelial defect measuring 2×3 mm and adjacent neovascularization. The anterior chamber was deep, with a 0.8 mm white hypopyon (Figure 1A). Fundus examination was unremarkable. The right eye had a poorly fitted ocular prosthesis with yellowish discharge from the orbital socket.

The patient was admitted, and scraping of the corneal infiltrate was performed for the left eye and sent for microbiological investigation (Gram staining, Giemsa Staining, and microbiological culture). The corneal scraping samples were collected by using a Kimura platinum spatula and inoculated on blood agar, chocolate agar, Sabouraud dextrose agar, and thioglyco-late broth by using standard C-streak method. Gram-negative bacilli were detected on Gram staining. Cultures of the corneal smear showed prominent growth of gram-negative bacilli on blood agar and chocolate agar. The isolated organism was confirmed to be Elizabethkingia meningoseptica. A conjunctival swab of the orbital socket was sent for microbiological investigation as well. The culture result from the conjunctival swab showed prominent growth of Elizabethkingia meningoseptica on blood and chocolate agar. The patient was prescribed fortified topical antibiotics consisting of cefazolin and ceftazidime (50 mg/ml) every hour. However, antimicrobial susceptibility testing indicated that the microbial isolate was resistant to ceftazidime and gentamicin, but was sensitive to fluoroquinolones. Therefore, topical moxifloxacin 0.50% was started every 4 hours in both eyes and with daily followup. The patient showed slow improvement. Topical fortified cefazoline and ceftazidime were tapered to every 4 hours then stopped after 4 days when the patient showed a clinical response to topical moxifloxacin. The patient was kept on topical moxifloxacin 0.50%. Topical prednisolone acetate 1% was started 4 times daily, 1 week after initiating moxifloxacin. The patient was discharged on prednisolone acetate 1%, 4 times daily, with tapering of the dose weekly; on topical moxifloxacin 0.50%, 4 times daily; and with eye lubricant ointment. Two weeks later, the patient’s visual acuity was 20/100. Examination of the eye revealed a healed corneal epithelial defect, resolved hypopyon, and corneal scarring (Figure 1B). After 2 months, the patient’s vision improved to 20/60. The graft was clear, with a faint superficial scar at the site of the previous infiltrate (Figure 1C).

Discussion

Elizabethkingia meningoseptica, which was formerly known as Flavobacterium meningosepticum and Chryseobacterium meningosepticum, is a nonfermenting, nonmotile, oxidase-positive, gram-negative bacterium that has been implicated in a variety of rare cases of meningitis, pneumonia, endocarditis, cellulitis, and sepsis [5]. E. meningoseptica is a rare opportunistic pathogen that is not part of the normal ocular flora. Few cases have been reported worldwide of ocular infections with Elizabethkingia sp. [6]. E. meningoseptica shows resistance to most of the first-line antibiotics used to treat gram-negative pathogens, including aminoglycosides, β-lactam antibiotics, tetracyclines, carbapenems, and chloramphenicol [5]. However, successful treatment with topical trimethoprim-sulfamethoxazole has been reported in the literature [6]. Additionally, previous studies have reported that E. meningoseptica is susceptible to cotrimoxazole, fluoroquinolones, minocycline, ticarcillin-clavulanate, piperacillin, and piperacillin-tazobactam [5]. Post-keratoplasty infectious keratitis can lead to significant ocular morbidity in the absence of timely and adequate treatment. Empirical broad-spectrum antimicrobials are the mainstay of treatment. Risk factors for microbial keratitis include prolonged contact lens use and ocular surface disease such as keratoconjunctivitis sicca [7–9]. Okonkwo et al evaluated 558 eyes after corneal graft and found that the most common predisposing factors for microbial keratitis were premorbid failed graft and topical anti-glaucoma treatment [9]. Infections of orbital implants have been previously reported in the literature. A retrospective study by Karslioglu et al of 212 patients with porous orbital implants reported that 11 (5.19%) patients had an implant infection [10]. The most common organisms grown from conjunctival cultures were Staphylococcus and Streptococcus species [10]. However, orbital socket infection secondary to prosthesis has not been reported as a risk factor for corneal infection of the contralateral eye. Microbial cultures and direct microscopic detection of the microorganisms are essential investigations to diagnose microbial keratitis. Microbial cultures can be reliable if growth of the same organism is observed on more than one solid-phase medium; if the growth of the microorganism is confluent at the site of inoculation on one solid medium; if growth on one medium is consistent with direct microscopy findings of Gram or Giemsa stain; and if the same organism is grown from repeated scrapings [11].

In the current case, the patient had a history of repeated penetrating keratoplasty in his seeing eye and he was on anti-glaucoma medications. His advanced age accompanied by a poor ocular surface may have predisposed the eye to infection with this opportunistic organism. The infection of the right orbital socket was transmitted to the left seeing eye, which indicates that proper care of the orbital socket and ocular prosthesis is essential to prevent transmission of infection from an ocular prosthesis to the contralateral seeing eye, especially in cases where ocular immunity is compromised. The growth of gram-negative bacilli was observed in 2 solid culture media and Gram stain. The E. meningoseptica we isolated was susceptible to fluoroquinolone and the patient responded to topical moxifloxacin 0.50%. To the best of our knowledge, there are no reports in the peer-reviewed literature of microbial keratitis with Elizabethkingia meningoseptica in a grafted eye secondary to a prosthesis infection of the fellow eye.

Conclusions

Microbial keratitis is a serious complication following penetrating keratoplasty. Prevention of infectious keratitis is essential and may be achieved by optimizing the ocular surface and treating the risk factors for infection. A high index of suspicion and timely diagnosis and management may improve the outcome and clinical response and reduce the morbidity associated with these infections. This case highlights the occur-rence of keratitis in a corneal graft secondary to an infection of the fellow orbital socket with the unusual organism E. meningoseptica, which was found to be sensitive to fluoroquino-lone. Further studies on orbital socket infection as a source of microbial keratitis in the contralateral eye are suggested.