Elizabethkingia is an important saprophyte that has grown much attention in recent years due to its ability to cause clinically significant infections and resistance to multiple anti-microbial agents [1–4]. Limited cases of ocular Elizabethkingia infections have been reported, where contact lens use, trauma, previous ocular surgery and ocular surface disorders appeared to be important risk factors [8–12]. We present the largest series of Elizabethkingia infection that has manifested in eyes. The spectrum of Elizabethkingia ocular infections is wide and mostly confined to the ocular surface. In our series, 40% (4/10) of cases resulted in keratitis, whereas 30% (3/10) caused conjunctivitis, 20% blepharitis (2/10) and 10% as concurrent blepharitis- conjunctivitis (1/10). The clinical characteristics of Elizabethkingia echoed with previous reports and is found confined to the ocular surface. Previously reported Elizabethkingia induced endophthalmitis was not found in our series and no intraocular infections were identified [13, 14]. To date, six species of Elizabethkingia have been identified: E. meningioseptica, E. miricola, E. anopheles, E. bruuniana, E. ursingii, and E. occultia . E. anopheles has traditionally been shown to be the predominant strain that causes life threatening bacteremia and neonatal meningitis, where E. meningoseptica and E. miricola are known to cause biliary tract infections . In our series, E. meningoseptica has been established to be the major species that caused ocular infection. The reason for the “ophthalmic strain” and predominance is unknown and yet to be determined.
The association of Elizabethkingia induced keratitis and contact lens is demonstrated in our study. Contact lens predisposes the cornea to microtrauma and hypoxia which disrupted the corneal epithelium and barrier to bacterial binding. In addition, biofilm formation and pathogen colonization on contact lens also potentiated the infection. This is confirmed in our study, where respective contact lens has cultured the same pathogen. The ability of Elizabethkingia to attach on contact lens, cases and water supplies is an important factor for development of ocular infections [3, 4]. Mechanisms including substandard contact lens hygiene, extended wear and trauma may also play a role in the potentiating the infection.
The association between orbital surgery and Elizabethkingia infection are also being reported for the first time. Previous reports have documented Elizabethkingia infections to occur after intraocular surgeries e.g. penetrating and lamellar keratoplasty [17, 18]. The authors believed history of previous orbital surgeries may be linked with development of ocular surface Elizabethkingia infections. In one of our case, an ocular prosthesis (scleral shell) presents as a risk factor for development of blepharitis in an eviscerated eye, as E. meningoseptica may have colonized the foreign body and acted as a reservoir for the pathogen. We speculate that the uneven surface of the acrylic prosthesis allowed bacterial attachment and subsequent biofilm formation, which created a barrier against removal from normal cleansing and sterilization.
The use of topical steroids in the post-operative cataract period may also be linked to E. meningoseptica blepharitis. Prolonged topical steroid was prescribed in our case due to anterior chamber inflammation. We suspect that the treatment aggravated the development of Elizabethkingia blepharitis, as topical steroid has been shown to delay epithelial healing and inhibit neutrophil activation, which subsequently weakened the ocular surface protective barrier [19, 20]. While chronic co-morbidities have been shown to cause Elizabethkingia systemic infections, in our study we could not establish a strong relationship, with only 40% (4/10) of cases identified to have significant past medical histories .
Established reports of antibiotics susceptibility on Elizabethkingia species have shown resistance to ceftazidime, imipenem and aminoglycosides and susceptibility to ciprofloxacin, cefoperazone-sulbactam and vancomycin treatments [16, 22, 23]. The multiple anti-microbial resistance in Elizabethkingia is conferred in β-lactams as a result of possession of Ambler class A serine extended-spectrum β-lactamase (ESBL) gene blaCME and Ambler class B metallo-β-lactamase (MBL) genes blaBlaB and blaGOB [24, 25]. Resistance is also seen in quinolones secondary to genetic mutations in DNA gyrase and topoisomerase IV . Empirical treatment using fluoroquinolone, glycopeptide and third-generation cephalosporin with β-lactamase inhibitor have been advocated for treating systemic infections [16, 22, 23].
There is currently no consensus on treatment for Elizabethkingia ophthalmic infections. Treatment of ocular infection frequently employ topical route of administration and susceptibility to commonly used topical antibiotics in ophthalmic practice, such as chloramphenicol and fusidic acid, have not been evaluated. Our series has demonstrated that combined use of 2 topical antibiotic, fluoroquinolone and chloramphenicol, could lead to safe and successful treatment of E. meningoseptica conjunctivitis, blepharitis and keratitis. The addition of systemic oral antibiotics such as oral quinolones, tetracycline or macrolide have shown to be effective. Levofloxacin, one of the commonly used topical fluoroquinolone in ophthalmological practice, contain a C-8 methoxy group that exert stronger antibacterial activity against fluoroquinolone-resistant bacteria that harbored QRDR mutations [27, 28]. Whether the single agent of topical fluroquinolone alone enabled treatment success or combination with topical chloramphenicol is not determined. Further studies are required to determine the susceptibility of chloramphenicol to Elizabethkingia species. A longer period of treatment for Elizabethkingia ocular surface infections was also observed, which averaged at 6.5 weeks in our series. We speculate that this could be due to bacterial intracellular invasion, inability to break multicellular biofilm and ineffective ocular immunity [3, 29]. This was reflected in the outcome, where conjunctivitis, blepharitis and conjunctivitis-blepharitis confer excellent clinical recovery where keratitis all resulted in corneal scarring.