B. cepacia is a rare causative agent of keratitis; only 8 cases of B. cepacia keratitis have been reported in previous studies (Table 2). B. cepacia accounted for 0.51% (5/875) of microbial keratitis cases in our previous 10-year (2003-2012) study [11], but we identified 12 more cases in recent years. To our best knowledge, this study is by far the largest case series related to B. cepacia keratitis. In conjunction with previously reported cases, we provided a more detailed overview of the clinical characteristics of B. cepacia keratitis.
In our study, the most common predisposing factor of B. cepacia keratitis was preexisting ocular disorder, particularly herpetic keratitis. Matoba also presented a patient with herpetic stroma keratitis, under oral acyclovir and topical prednisolone acetate treatment, who developed polymicrobial keratitis including B. ambifaria (belonging to the B. cepacia complex), Enterococcus spp., and Staphylococcus aureus [7]. Infection with herpes virus might cause sub-basal nerve damage of the cornea [12, 13]. The impaired corneal sensory innervation leads to a reduction of protective reflexes and trophic neuromodulators, which affect the wound-healing function of the cornea [14], making its surface an easy target for opportunistic bacteria such as B. cepacia. In addition, if the local immune response has been suppressed by topical steroids, a herpetic corneal ulcer can predispose microbial adherence, furthering the infection. Recent ocular surgery with simultaneous topical steroid use was noted in 3 of the previously reported 8 patients with B. cepacia keratitis and 2 patients in our study (Tables 1 and 2), suggesting that local immunosuppression may play a role in such an opportunistic infection.
In our study, approximately 40% of B. cepacia culture-positive corneal scrapings were polymicrobial, as were 2 (25%) of the previously reported 8 cases (Table 2). These mixed infections might be due to direct inoculation because of a corneal injury, contamination through the process of corneal scraping, or opportunistic transmission in these immunocompromised patients [15]. Tuft proposed a synergy effect of interactions between organisms in polymicrobial infection[16] and speculated that the primary organism may create a niche, either by providing a sequestered environment or by supplying specific metabolic requirements for a second organism, that predisposes the host to further infection or turns a normally nonpathogenic organism into a pathogen. The mixed infections might modulate the clinical course of the disease, causing unexpected treatment effects.
B. cepacia demonstrates multidrug resistance, including resistance to carboxypenicillins, polymyxins, and aminoglycosides. Nevertheless, sulfamethoxazole–trimethoprim, ceftazidime, and meropenem have been revealed to be the most effective agents on the basis of in vitro susceptibility data, which agrees with our drug susceptibility test results [17]. We did not test for susceptibility to fluoroquinolones, the most popular empiric antibiotic in the field of ophthalmology. Chaurasia et al. performed an antibiotic susceptibility test for 4 B. cepacia isolated from keratitis and reported 100% susceptibility to ceftazidime and 50% susceptibility to ciprofloxacin/norfloxacin [4]. In the case report by Reddy et al., the isolate from the patient with B. cepacia keratitis was resistant to moxifloxacin, gatifloxacin, tobramycin, and ceftazidime and susceptible only to sulfamethoxazole–trimethoprim in vitro; nevertheless, in vivo, the ulcer resolved completely after tobramycin and gatifloxacin treatment (Table 2) [9]. The other 3 isolates from previously reported B. cepacia keratitis cases were susceptible to ceftazidime and ciprofloxacin [5, 7, 18]. On the basis of the antibiotic susceptibility and clinical results of the patients with B. cepacia keratitis (Tables 1 and 2), fluoroquinolones could be initiated as empiric antibiotics. However, if fluoroquinolone use does not improve the clinical course, ceftazidime may be a suitable alternative. Even after aggressive medical treatment, about one-third of the patients in our study and 2 (25%) of the previously reported 8 B. cepacia keratitis cases required surgical interventions (Tables 1 and 2).
The visual outcome of B. cepacia keratitis was generally poor both in our and previously reported cases (Tables 1 and 2). The unfavorable visual outcomes may be related to old age, poor vision at presentation, comorbidities, and mixed infections. The rather high surgical rates and perforation rates may also contribute to the poor prognosis of the disease.
The retrospective design and small sample size are the limitations of this study. In addition, elucidating the real pathogenic role of B. cepacia was difficult because polymicrobial infections were detected in approximately 40% of our patients. Nevertheless, as the largest case series reporting B. cepacia keratitis, this study provides more detailed information regarding the clinical and microbiological profiles of this infection.
In conclusion, although relatively uncommon, B. cepacia could be a causative agent of infectious keratitis. Our findings revealed that preexisting ocular disease, particularly herpetic keratitis, was the leading predisposing factor of B. cepacia keratitis. B. cepacia demonstrated clinical response to ceftazidime and fluoroquinolone, but some patients required surgical intervention. However, the visual outcome was generally poor.